| 1. |
- Bartholeyns, J, et al.
(författare)
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Cellular vaccines
- 1998
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Ingår i: Research in Immunology. - 0923-2494 .- 1879-1425. ; 149, s. 647-649
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Tidskriftsartikel (refereegranskat)abstract
- This project is devoted to the development of novel cellular vaccines designed to treat cancer patients. These cellular vaccines present and enhance immunogens, which will elicit a potent immune response. The goal is to achieve safe and effective immune reaction against the patient's own tumour. (1) Autologous cellular vaccines are prepared by processing circulating brood mononuclear cells outside of the patient's body (ex vivo) to differentiate them into antigen-presenting cells (APCs). Monocyte-derived APCs (MD-APCs) are then grown in the presence of exogenous target antigens (tumour cell debris, or apoptotic bodies) to become fully mature APCs. (2) Functionality for antigen presentation to T cells of ex vivo MD-APCs is evaluated in vivo. (3) Cellular vaccines are tested in selected rodent animal models. Efficiency and immune response are monitored in pertinent experimental systems for cancer. Pharmacological data are generated for clinical investigation. Tolerance and biologic effects are documented in primates. (4) The first clinical trials on cancer patients are taking place in 1998 on melanoma and prostate cancer to validate the concept. Specialized eel processors with dedicated software and standardized controls are being developed and used for the preparation of cellular vaccines. (5) The evaluation of new non-viral vectors and the validation of new non-viral transfection methods of mononuclear cells with marker genes is in progress and will lead to the ex vivo transfection of genes coding for immunostimulating cytokines or for tumour antigens in MD-APCs. Efficiency will be validated in vitro and in animal models. The ex vivo and animal model studies validate the clinical relevance of this new cellular immunotechnology. Clinical validation of individual autologous cellular vaccines in specific indications for which no treatment is presently available will allow the development of cellular and gene immunotherapy for other types of cancers.
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| 2. |
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| 3. |
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| 4. |
- Malmsten, M, et al.
(författare)
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Adsorption of apolipoprotein B at phospholipid model surfaces
- 1995
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Ingår i: Journal of Colloid and Interface Science. - 0021-9797 .- 1095-7103. ; 172, s. 485-493
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Tidskriftsartikel (refereegranskat)abstract
- The adsorption of apolipoprotein B (Apo B) at a series of surfaces was investigated with in situ ellipsometry. For silica and methylated silica, the adsorbed amount (G), the adsorbed layer thickness (del) and the mean adsorbed layer refractive index (nf) were obtained by a procedure involving studies of the bare substrate at two different ambient refractive indices, as well as four-zone averaging. The adsorbed amount of Apo B is much higher at silica than at methylated silica. Despite this, the adsorbed layer thickness is the same at the two surfaces, and the adsorbed layer formation proceeds similarly. In both cases, the adsorbed layer formation occurs through the adsorption of Apo B molecules in an essentially random orientation, the difference between silica and methylated silica being the number of molecules adsorbed per unit area. Furthermore, the adsorption of Apo B at phospholipid surfaces was investigated. It was found that the adsorption at phosphatidylcholine (PC) was quite limited, whereas that at phosphatidic acid (PA) was substantial. Studies with mixed PA/PC layers showed that the Apo B adsorption depends on the mixed phospholipid layer composition in an essentially linear fashion. Finally, mixed phospholipid layers of PC and ganglioside GM1, as well as phosphatidylinositol (PI) layers, showed a dramatic preferential adsorption of Apo B over, e. g. human serum albumin (HSA), IgG, fibronectin and fibrinogen.
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| 5. |
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| 6. |
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| 7. |
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| 8. |
- Jing, Xiaona, et al.
(författare)
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Delivery of siRNA Complexed with Palmitoylated alpha-Peptide/beta-Peptoid Cell-Penetrating Peptidomimetics : Membrane Interaction and Structural Characterization of a Lipid-Based Nanocarrier System
- 2016
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Ingår i: Molecular Pharmaceutics. - : American Chemical Society (ACS). - 1543-8384 .- 1543-8392. ; 13:6, s. 1739-1749
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Tidskriftsartikel (refereegranskat)abstract
- Proteolytically stable alpha-peptide/beta-peptoid peptidomimetics constitute promising cell-penetrating carrier candidates exhibiting superior cellular uptake as compared to commonly used cell-penetrating peptides (CPPs). The aim of the present study was to explore the potential of these peptidomimetics for delivery of small interfering RNA (siRNA) to the cytosol by incorporation of a palmitoylated peptidomimetic construct into a cationic lipid-based nanocarrier system. The optimal construct was selected on the basis of the effect of palmitoylation and the influence of the length of the peptidomimetic on the interaction with model membranes and the cellular uptake. Palmitoylation enhanced the peptidomimetic adsorption to supported lipid bilayers as studied by ellipsometry. However, both palmitoylation and increased peptidomimetic chain length were found to be beneficial in the cellular uptake studies using fluorophore-labeled analogues. Thus, the longer palmitoylated peptidomimetic was chosen for further formulation of siRNA in a dioleoylphosphatidylethanolamine/cholesteryl hemisuccinate (DOPE/CHEMS) nanocarrier system, and the resulting nanoparticles were found to mediate efficient gene silencing in vitro. Cryo-transmission electron microscopy (cryo-TEM) revealed multilamellar, onion-like spherical vesicles, and small-angle X-ray scattering (SAXS) analysis confirmed that the majority of the lipids in the nanocarriers were organized in lamellar structures, yet coexisted with a hexagonal phase, which is important for efficient nanocarrier-mediated endosomal escape of siRNA ensuring cytosolic delivery. The present work is a proof-of-concept for the use of alpha-peptides/beta-peptoid peptidomimetics in an efficient delivery system that may be more generally exploited for the intracellular delivery of biomacromolecular drugs.
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| 9. |
- Malekkhaiat Häffner, S., et al.
(författare)
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Composition effects on photooxidative membrane destabilization by TiO2 nanoparticles
- 2021
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Ingår i: Journal of Colloid and Interface Science. - : Elsevier BV. - 0021-9797. ; 584, s. 19-33
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Tidskriftsartikel (refereegranskat)abstract
- Membrane interactions and photooxidative membrane destabilization of titanium dioxide (TiO2) nanoparticles were investigated, focusing on the effects of membrane composition, notably phospholipid headgroup charge and presence of cholesterol. For this, we employed a battery of state-of-the-art methods for studies of bilayers formed by zwitterionic palmitoyloleoylphosphatidylcholine (POPC) containing also polyunsaturated palmitoylarachidonoylphosphocholine (PAPC), as well as its mixtures with anionic palmitoyloleoylphosphatidylglycerol (POPG) and cholesterol. It was found that the TiO2 nanoparticles display close to zero charge at pH 7.4, resulting in aggregation. At pH 3.4, in contrast, the 6 nm TiO2 nanoparticles are well dispersed due to a strongly positive ζ-potential. Mirroring this pH dependence, TiO2 nanoparticles were observed to bind to negatively charged lipid bilayers at pH 3.4, but much less so at pH 7.4. While nanoparticle binding has some destabilizing effect alone, illumination with ultraviolet (UV) light accentuates membrane destabilization, a result of oxidative stress caused by generated reactive oxygen species (ROS). Neutron reflectivity (NR), quartz crystal microbalance (QCM), and small-angle X-ray scattering (SAXS) results all demonstrate that membrane composition strongly influences membrane interactions and photooxidative destabilization of lipid bilayers. In particular, the presence of anionic POPG makes the bilayers more sensitive to oxidative destabilization, whereas a stabilizing effect was observed in the presence of cholesterol. Also, structural aspects of peroxidation were found to depend strongly on membrane composition, notably the presence of anionic phospholipids. The results show that membrane interactions and UV-induced ROS generation act in concert and need to be considered together to understand effects of lipid membrane composition on UV-triggered oxidative destabilization by TiO2 nanoparticles, e.g., in the context of oxidative damage of bacteria and cells.
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| 10. |
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| 11. |
- Scherlund, M, et al.
(författare)
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Local anaesthetic block copolymer system undergoing phase transition on dilution with water
- 2001
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Ingår i: European Journal of Pharmaceutical Sciences. - 0928-0987 .- 1879-0720. ; 14, s. 53-61
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Tidskriftsartikel (refereegranskat)abstract
- The possibility of formulating a local anaesthetic system displaying in situ gelation on dilution with water, as well as its dependence on concentration of active ingredients and pH was investigated. For this purpose Lutrol F68, water, a eutectic mixture of lidocaine and prilocaine and Akoline MCM were mixed in different ratios and investigated using crossed polarisers, small-angle X-ray diffraction, rheology, conductivity and NMR self-diffusion measurements. In particular, an isotropic phase of low viscosity turning into a high viscous hexagonal phase upon dilution with water was found. The increase in viscosity is only weakly dependent on temperature in the temperature range of 20-37 degrees C. The rheology and in vitro drug release of these systems were studied and the elastic modulus was found to be fairly independent of concentration of active ingredients and pH in the investigated region. The in vitro release of lidocaine and prilocaine was found to increase with increasing concentration of the active ingredients and with decreasing pH, the latter as a consequence of the pH-dependent ionisation of these substances. The behaviour of the system is promising from a pharmaceutical point of view, since the isotropic low-viscous phase can be injected into, e.g. a periodontal pocket where the presence of saliva will cause a temporal transition into a rigid hexagonal phase thus making the formulation stay at the application site. At even higher water content, either as a result of longer application time or rinsing with water, the hexagonal phase is effectively dissolved through transformation to a water-rich micellar phase
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| 12. |
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| 13. |
- Scherlund, M, et al.
(författare)
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Micellization and gelation in block copolymer systems containing local anesthetics
- 2000
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Ingår i: International Journal of Pharmaceutics. - 0378-5173 .- 1873-3476. ; 211, s. 37-49
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Tidskriftsartikel (refereegranskat)abstract
- A formulation consisting of a eutectic mixture of lidocaine and prilocaine, Lutrol(R) F68 and Lutrol(R) F127, suitable for anesthetizing the periodontal pocket has previously been developed. This consists of discrete micelles with a diameter of 20-30 nm and has a suitable gelation temperature, a good release profile and excellent long-term stability. In this study, the unimer/micelle transition and gel formation of the formulation, in its concentrated state, are investigated using differential scanning calorimetry (DSC), dye solubilization, rheology, and nuclear magnetic resonance (NMR) self-diffusion. The critical micellization temperature (cmt) and gelation temperature are found to be interconnected and influenced by cosolutes, such as electrolytes and hydrophobic substances, the latter as found particularly for the eutectic mixture of the local anesthetic agents lidocaine and prilocaine. Both cmt and the gelation temperature decrease with increasing pH of the system, i.e. at reduced solubility of the active ingredients. Moreover, both cmt and the gelation temperature increase upon diluting the system with water. The ratio between the two block copolymers present in the system also has an impact on both cmt and the gelation temperature, resulting in a decrease in onset tt temperature of both processes with an increase of Lutrol(R) F127, The amount of the active ingredients present in the micelle phase depends on the pH of thc system bring approximately 0% w/w at pH 5, 50-60% w/w at pH 7.8 and 80% w/w at pH 9.
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| 14. |
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| 15. |
- Scherlund, M, et al.
(författare)
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Nonionic cellulose ethers as potential drug delivery systems for periodontal anesthesia
- 2000
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Ingår i: Journal of Colloid and Interface Science. - 0021-9797 .- 1095-7103. ; 229, s. 365-374
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Tidskriftsartikel (refereegranskat)abstract
- Nonionic cellulose ethers displaying a lower consolute temperature, or cloud-point, close to body temperature were investigated as potential carrier systems for the delivery of local anesthetic agents to the periodontal pocket. The interaction between the polymers, i.e., ethyl(hydroxyethyl)cellulose (EHEC) and hydrophobically modified EHEC (HM-EHEC), and ionic surfactants was determined in the absence and in the presence of the local anesthetic agents lidocaine and prilocaine. The cloud-point and rheology data indicate interactions between the polymer and both anionic and cationic surfactants. More precisely, a number of ionic surfactants were found to result in an increase in cloud-point at higher surfactant concentrations, a surfactant-concentration-dependent thickening, and a temperature-induced gelation upon heating. Upon addition of the local anesthetic agents lidocaine and prilocaine in their uncharged form to EHEC and HM-EHEC, in the absence of surfactants, only minor interaction with the polymer could be inferred. However, these substances were found to affect the polymer-surfactant interaction. In particular, the drug release rate in vitro as well as the stability and temperature-dependent viscosity were followed for an EHEC/SDS system and EHEC/myristoylcholine bromide system upon addition of lidocaine and prilocaine. The data indicate a possibility of formulating a local anesthetic drug delivery system suitable for administration into the periodontal pocket where at least small amounts of active ingredients can be incorporated into the system without severely affecting the gelation behavior. The results found for the cationic myristoylcholine bromide system are particularly interesting for the application in focus here since this surfactant is antibacterial and readily biodegradable.
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| 16. |
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| 17. |
- Scherlund, M, et al.
(författare)
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Stabilization of a thermosetting emulsion system using ionic and nonionic surfactants
- 1998
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Ingår i: International Journal of Pharmaceutics. - 0378-5173 .- 1873-3476. ; 173, s. 103-116
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Tidskriftsartikel (refereegranskat)abstract
- Ways of achieving a suitable local anesthetic formulation for use in the periodontal cavity were investigated in this study. By choosing poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) block copolymers as excipients, formulations which are low viscosity fluids at room temperature and rigid elastic gels at body temperature are obtained. Despite the solubilizing capacity of these polymers, formulations containing Lutrol(R) F127 (EO99PO65EO99) and the active ingredients lidocaine and prilocaine at the desired concentrations, i.e. approximately 25 mg g(-1) of each component, are unstable. In order to achieve a more stable formulation a second surfactant can be added to the system since it could help both to solubilize the hydrophobic active ingredients and to stabilize the droplets of lidocaine and prilocaine from flocculation and coalescence. Thus, formulations containing local anesthetic compounds comprising the oil phase, a block copolymer giving the system unique rheological properties, and a suitable second surfactant were evaluated with regard to rheological behavior, drug release properties and stability. The system needs to be balanced regarding the concentration of polymer, active ingredients and surfactant in order to achieve a formulation with suitable properties. Stable formulations with appropriate characteristics for the application in focus here were obtained with anionic, cationic and nonionic surfactants.
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| 18. |
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| 19. |
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| 20. |
- Schillén, Karin, et al.
(författare)
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Properties of poly(ethylene oxide)-poly(butylene oxide) diblock copolymers at the interface between hydrophobic surfaces and water
- 1997
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Ingår i: Journal of Physical Chemistry B. - : American Chemical Society (ACS). - 1520-6106 .- 1520-5207. ; 101, s. 4238-4252
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Tidskriftsartikel (refereegranskat)abstract
- The interaction between molecules of a low molecular weight diblock copolymer of poly(ethylene oxide) (E) and poly(butylene oxide) (B), B8E41, at hydrophobic surfaces were investigated experimentally by using two surface force techniques and ellipsometry. Extended mean-field theory was employed to describe the adsorption of EB diblock copolymers at planar surfaces as well as the forces between surfaces with adsorbed diblock copolymers. It is the hydrophobic poly(butylene oxide) block that anchors the diblock copolymer at the hydrophobic surface with the water-soluble poly(ethylene oxide) block protruding in the aqueous solution in a "brushlike" or at least streched structure. The adsorption kinetics demonstrate that two adsorption regimes exist, one which is transport-limited and the other at higher adsorption where a slower branch due to crowding effects at the surface exists. Only monotonic repulsuve steric forces between the diblock copolymer-coated surfaces were observed in the surface force measurements. The range of the steric repulsion increased with increasing bulk copolymer concentration, whereas the concentration of an inert salt (KBr, up to 0.1 M) did not influence the measured steric interaction. Upon dilution the block copolymer slowly dissolved, which resulted in a less long-range steric force, and under a high force the layers were squeezed out from between the surfaces. The adsorbed layer thickness obtained in the experiments varied with solution volume-to-surface area ratio. This is interpreted as being caused by the polydispersity of the diblock copolymer. The interaction parameters entering the mean-field model were fitted to reproduce adsorption isotherms of the diblock copolymer and of two triblock copolymers of different architectures. Calculations were performed for mondisperse and polydisperse diblock copolymers. The agreement between theory and experiment was improved when the molecular polydispersity (Mm/Mn = 1.1) of the sample was taken into account. In particular, polydispersity led to predicted adsorption isotherms that are more of the high affinity type and more sensitive to low volume-to-surface area ratio and to the interaction between surfaces starting at a longer separation. Among the polymer components, it is those with the largest B block that adsorb preferentially, which leads to an increased amount adsorbed and forces the E chains to adopt more extended conformations.
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| 21. |
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| 22. |
- Siegel, G, et al.
(författare)
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Anionic biopolymers as blood flow sensors
- 1996
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Ingår i: Biosensors & bioelectronics. - 0956-5663 .- 1873-4235. ; 11, s. 281-294
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Tidskriftsartikel (refereegranskat)abstract
- The finding of flow-dependent vasodilatation rests on the basic observation that with an increase in blood flow the vessels become wider, with a decrease the vascular smooth muscle cells contract. Proteoheparan sulphate could be the sensor macromolecule at the endothelial cell membrane-blood interface, that reacts on the shear stress generated by the flowing blood, and that informs and regulates the vascular smooth muscle cells via a signal transduction chain. This anionic biopolyelectrolyte possesses viscoelastic and specific ion binding properties which allow a change of its configuration in dependence on shear stress and electrostatic charge density. The blood flow sensor undergoes a conformational transition from a random coil to an extended filamentous state with increasing flow, whereby Na+ ions from the blood are bound. Owing to the intramolecular elastic recoil forces of proteoheparan sulphate the slowing of a flow rate causes an entropic coiling the expulsion of Na+ ions and thus an interruption of the signal chain. Under physiological conditions, the conformation and Na+ binding proved to be extremely Ca2+-sensitive while K+ and Mg2+ ions play a minor role for the susceptibility of the sensor. Via counterion migration of the bound Na+ ions along the sensor glycosaminoglycan side chains and following Na+ passage through an unspecific ion channel in the endothelial cell membrane, the signal transduction chain leads to a membrane depolarization with Ca2+ influx into the cells. This stimulates the EDRF/NO production and release from the endothelial cells. The consequence is vasodilatation.
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| 23. |
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| 24. |
- Siegel, G., et al.
(författare)
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Nanotechnologic biosensor ellipsometry and biomarker pattern analysis in the evaluation of atherosclerotic risk profile.
- 2009
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Ingår i: Biosensors & bioelectronics. - : Elsevier BV. - 1873-4235 .- 0956-5663. ; 24:5, s. 1512-1517
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Tidskriftsartikel (refereegranskat)abstract
- A proteoheparan sulfate coated, hydrophobic silica surface serves as lipoprotein receptor at which the Ca(2+)-driven arteriosclerotic nanoplaque formation can be pursued by laser-based ellipsometry. Any lipoprotein from human blood can be very sensitively tested for its atherogenic properties. From the same blood sample, it is possible to determine the concentration and activity of a series of interacting biomarker molecules which, through a pattern analysis, allow to assess the state of health with respect to cardiovascular diseases. These two interlinked and complementary biosensors make a prospective cardio-cerebro-vascular risk stratification feasible, especially the sequelae of an underlying arteriosclerotic disease. Based on these diagnostic tools, an optimized therapy decision for the patient can be taken and the necessary preventive measures for the still healthy person.
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| 25. |
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| 26. |
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| 27. |
- Abletshauser, C, et al.
(författare)
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Biosensing of arteriosclerotic nanoplaque formation and interaction with an HMG-CoA reductase inhibitor
- 2002
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Ingår i: Acta Physiologica Scandinavica. - 0001-6772 .- 1365-201X. ; 176, s. 131-146
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Tidskriftsartikel (refereegranskat)abstract
- Proteoheparan sulphate can be adsorbed to a methylated silica surface in a monomolecular layer via its transmembrane hydrophobic protein core domain. As a result of electrostatic repulsion, its anionic glycosaminoglycan side chains are stretched out into the blood substitute solution, thereby representing one receptor site for specific lipoprotein binding through basic amino acid-rich residues within their apolipoproteins. The binding process was studied by ellipsometric techniques suggesting that high-density lipoprotein (HDL) has a high binding affinity and a protective effect on interfacial heparan sulphate proteoglycan layers with respect to low-density lipoprotein (LDL) and Ca2+ complexation. Low-density lipoprotein was found to deposit strongly at the proteoheparan sulphate-coated surface, particularly in the presence of Ca2+, apparently through complex formation 'proteoglycan-LDL-calcium'. This ternary complex build-up may be interpreted as arteriosclerotic nanoplaque formation on the molecular level responsible for the arteriosclerotic primary lesion. On the other hand, HDL bound to heparan sulphate proteoglycan protected against LDL deposition and completely suppressed calcification of the proteoglycan-lipoprotein complex. In addition, HDL was able to decelerate the ternary complex deposition. Therefore, HDL attached to its proteoglycan receptor sites is thought to raise a multidomain barrier, selection and control motif for transmembrane and paracellular lipoprotein uptake into the arterial wall. Although much remains unclear regarding the mechanism of lipoprotein depositions at proteoglycan-coated surfaces, it seems clear that the use of such systems offers possibilities for investigating lipoprotein deposition at a 'nanoscopic' level under close to physiological conditions. In particular, Ca2+-promoted LDL deposition and the protective effect of HDL even at high Ca2+ and LDL concentrations agree well with previous clinical observations regarding risk and beneficial factors for early stages of atherosclerosis. Considering this, the system was tested on its reliability in a biosensor application in order to unveil possible acute pleiotropic effects of the lipid lowering drug fluvastatin. The very low-density lipoprotein (VLDL)/intermediate-density lipoprotein (IDL)/LDL plasma fraction from a high risk patient with dyslipoproteinaemia and type 2 diabetes mellitus showed beginning arteriosclerotic nanoplaque formation already at a normal blood Ca2+ concentration, with a strong increase at higher Ca2+ concentrations. Fluvastatin, whether applied to the patient (one single 80 mg slow release matrix tablet) or acutely in the experiment (2.2 μmol L-1), markedly slowed down this process of ternary aggregational nanoplaque complexation at all Ca2+ concentrations used. This action resulted without any significant change in lipid concentrations of the patient. Furthermore, after ternary complex build-up, fluvastatin, similar to HDL, was able to reduce nanoplaque adsorption and size. These immediate effects of fluvastatin have to be taken into consideration while interpreting the clinical outcome of long-term studies.
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| 28. |
- Browning, Kathryn L., et al.
(författare)
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Effect of bilayer charge on lipoprotein lipid exchange
- 2018
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Ingår i: Colloids and Surfaces B. - : ELSEVIER SCIENCE BV. - 0927-7765 .- 1873-4367. ; 168, s. 117-125
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Tidskriftsartikel (refereegranskat)abstract
- Lipoproteins play a key role in the onset and development of atherosclerosis, the formation of lipid plaques at blood vessel walls. The plaque formation, as well as subsequent calcification, involves not only endothelial cells but also connective tissue, and is closely related to a wide range of cardiovascular syndromes, that together constitute the number one cause of death in the Western World. High (HDL) and low (LDL) density lipoproteins are of particular interest in relation to atherosclerosis, due to their protective and harmful effects, respectively. In an effort to elucidate the molecular mechanisms underlying this, and to identify factors determining lipid deposition and exchange at lipid membranes, we here employ neutron reflection (NR) and quartz crystal microbalance with dissipation (QCM-D) to study the effect of membrane charge on lipoprotein deposition and lipid exchange. Dimyristoylphosphatidylcholine (DMPC) bilayers containing varying amounts of negatively charged dimyristoylphosphatidylserine (DMPS) were used to vary membrane charge. It was found that the amount of hydrogenous material deposited from either HDL or LDL to the bilayer depends only weakly on membrane charge density. In contrast, increasing membrane charge resulted in an increase in the amount of lipids removed from the supported lipid bilayer, an effect particularly pronounced for LDL. The latter effects are in line with previously reported observations on atherosclerotic plaque prone regions of long-term hyperlipidaemia and type 2 diabetic patients, and may also provide some molecular clues into the relation between oxidative stress and atherosclerosis.
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| 29. |
- Browning, Kathryn L., et al.
(författare)
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Human Lipoproteins at Model Cell Membranes : Effect of Lipoprotein Class on Lipid Exchange
- 2017
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- High and low density lipoproteins (HDL and LDL) are thought to play vital roles in the onset and development of atherosclerosis; the biggest killer in the western world. Key issues of initial lipoprotein (LP) interactions at cellular membranes need to be addressed including LP deposition and lipid exchange. Here we present a protocol for monitoring the in situ kinetics of lipoprotein deposition and lipid exchange/removal at model cellular membranes using the non-invasive, surface sensitive methods of neutron reflection and quartz crystal microbalance with dissipation. For neutron reflection, lipid exchange and lipid removal can be distinguished thanks to the combined use of hydrogenated and tail-deuterated lipids. Both HDL and LDL remove lipids from the bilayer and deposit hydrogenated material into the lipid bilayer, however, the extent of removal and exchange depends on LP type. These results support the notion of HDL acting as the 'good' cholesterol, removing lipid material from lipid-loaded cells, whereas LDL acts as the 'bad' cholesterol, depositing lipid material into the vascular wall.
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| 30. |
- Browning, T. K., et al.
(författare)
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Human lipoproteins at model cell membranes : Role of the lipoprotein class on lipid dynamics
- 2017
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- High and low density lipoproteins (HDL and LDL) are thought to play vital roles in the onset and development of atherosclerosis; the biggest killer in the western world. Key issues of initial lipoprotein (LP) interactions at cellular membranes need to be addressed including LP deposition and lipid exchange. Here we present a protocol for monitoring the in situ kinetics of lipoprotein deposition and lipid exchange/removal at model cellular membranes using the non-invasive, surface sensitive methods of neutron reflection and quartz crystal microbalance with dissipation. For neutron reflection, lipid exchange and lipid removal can be distinguished thanks to the combined use of hydrogenated and tail-deuterated lipids. Both HDL and LDL remove lipids from the bilayer and deposit hydrogenated material into the lipid bilayer, however, the extent of removal and exchange depends on LP type. These results support the notion of HDL acting as the ‘good’ cholesterol, removing lipid material from lipid-loaded cells, whereas LDL acts as the ‘bad’ cholesterol, depositing lipid material into the vascular wall.
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| 31. |
- Carlsson, F, et al.
(författare)
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Interactions between local anaesthetic agents and poly(N-isopropyl acrylamide) through phase behavior, surface tension, and adsorption measurements
- 2001
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Ingår i: Journal of Colloid and Interface Science. - 0021-9797 .- 1095-7103. ; 233, s. 320-328
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Tidskriftsartikel (refereegranskat)abstract
- he interaction between the local anaesthetic agents prilocaine and lidocaine, on one hand, and poly(N-isopropyl acrylamide) (pNIPAM), on the other, is investigated through studies of the polymer phase behavior and through surface tension and adsorption measurements. In particular, the cloud points (CP) for pNIPAM in the presence of lidocaine and prilocaine under different conditions were compared to the effects of electrolytes and alcohols. It was found that the electrolytes affect the CP of pNIPAM in a lyotropic manner, whereas alcohols depress the CP of pNIPAM in an alkyl chain length dependent way; i.e., the longer the chain, the larger the decrease in CP. Lidocaine and prilocaine affect the CP of pNIPAM in a pH-dependent manner. Below the p Ka of lidocaine and prilocaine, these cosolutes do not substantially affect the CP in the concentration range investigated, but rather behave analogous to simpler electrolytes. Above the p Ka, on the other hand, they strongly depress the CP already at low concentrations. In parallel, at low pH, the surface tension reduction due to lidocaine or prilocaine is marginal, whereas at high pH the surface tension is reduced considerably. Thus, the poor solubility of prilocaine and lidocaine at high pH causes these to become more surface active and simultaneously interact in a more pronounced way with pNIPAM. Furthermore, it was found from ellipsometry that an adsorbed pNIPAM layer contracts when lidocaine is added, presumably due to a lidocaine-pNIPAM interaction similar to that causing pNIPAM to phase separate. Analogous to this, it was demonstrated that an adsorbed pNIPAM layer shrinks and swells reversibly when the temperature is cycled above and beneath the CP.
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| 32. |
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| 33. |
- Carlsson, F, et al.
(författare)
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Lysozyme adsorption to charged surfaces. A Monte Carlo study
- 2004
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Ingår i: The Journal of Physical Chemistry Part B. - : American Chemical Society (ACS). - 1520-5207 .- 1520-6106. ; 108, s. 9871-
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Tidskriftsartikel (refereegranskat)abstract
- Lysozyme adsorption to charged surfaces was studied by Monte Carlo simulations at different protein concentrations, protein net charges, ionic strengths, and surface charge densities. The lysozyme was represented by a hard sphere with embedded positive and negative surface charges parametrically dependent on the solution pH. A short-range attractive protein-protein potential was included to represent attractive non-Coulomb forces. The charged surface was described by a hard wall with embedded charges representing a mica surface. The protein adsorption was favored by high protein concentration, high protein net charge, low ionic strength, and high surface charge density. Nevertheless, adsorption appeared also for a weakly negatively charged protein to the negatively charged surface as a result of an electrostatically favorable protein orientation at the surface. While a multipole expansion including monopole and dipole moments only was insufficient to explain preferential orientation, an expansion including also quadrupole moments provided a satisfactory picture. Finally, it was found that the short-range attraction between the proteins increased the adsorbed amount, as well as the structure in the adsorbed protein layer. The adsorbed amounts obtained compared favorably with experimental results.
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| 34. |
- Carlsson, F, et al.
(författare)
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Monte Carlo simulations of lysozyme self-association in aqueous solution
- 2001
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Ingår i: Journal of Physical Chemistry B. - 1520-6106 .- 1520-5207. ; 105, s. 12189-12195
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Tidskriftsartikel (refereegranskat)abstract
- The oligomerization of lysozyme in aqueous solution was investigated by Monte Carlo simulations as a function of protein concentration, pH, and electrolyte screening. Lysozyme was modeled as a hard sphere with embedded pH-dependent discrete charges and with an attractive 1/r6-potential representing nonspecific short-range attraction. The magnitude of the 1/r6-potential was adjusted to reproduce experimental second virial coefficients. Radial distribution functions, structure factors, cluster size distributions, and orientation correlations were determined at various conditions. It was observed that increasing protein concentration, or decreasing the electrostatic repulsion between protein molecules by either reducing the protein charge or increasing the ionic strength, promoted cluster formation. Structure factors and equilibrium constants obtained were compared to those obtained experimentally and were found to capture the experimentally obtained effects of pH and ionic strength. The influence of the location of the hydrophobic site was also examined
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| 35. |
- Carlsson, F, et al.
(författare)
-
Monte Carlo simulations of polyelectrolyte-protein complexation
- 2001
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Ingår i: Journal of Physical Chemistry B. - 1520-6106 .- 1520-5207. ; 105, s. 9040-9049
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Tidskriftsartikel (refereegranskat)abstract
- The complexation between one polyelectrolyte and one protein has been examined by employing a simple model system solved by Monte Carlo simulations. The polyelectrolyte was composed of a sequence of negatively charged hard spheres, and the protein was represented by a hard sphere with embedded pH-dependent discrete charges, the positions of which were taken from lysozyme. A short-range attractive interaction between the polyelectrolyte and the protein accounting for hydrophobic interactions completed the model. The complexation was found to depend decisively on the charge status of the protein model as well as on the presence of the short-range attractive interaction. In particular, the complexation weakens at decreasing ionic strength except for the highest positive protein net charge considered, and in the absence of the short-range attraction, a positively charged protein was required to obtain a complex. The distribution of the polyelectrolyte beads was inhomogeneous at the protein surface, and the polyelectrolyte contracted upon complexation. Finally, the protein model with discrete charges gave a stronger complex than the corresponding protein model with a homogeneous surface charge density.
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| 36. |
- Claesson, PM, et al.
(författare)
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Adsorption and interaction of a graft copolymer of poly(ethylene imine) and poly(ethylene oxide)
- 1996
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Ingår i: Colloids and Surfaces A. - 0927-7757 .- 1873-4359. ; 112, s. 131-139
-
Tidskriftsartikel (refereegranskat)abstract
- The adsorption of proteins and particles onto surfaces carrying firmly adsorbed or covalently bound chains of poly(ethylene oxide) (PEO) is generally very low. This makes it of fundamental and practical interest to learn about the structure of PEO-coatings and how PEO-coated surfaces interact with each other and e.g. proteins. A prerequisite for such studies is, of course, that stable PEO-coated surfaces can be obtained. For this purpose we employed a two-step method to coat negatively charged surfaces, such as mica or silica, with PEO. In the first reaction step, cationic poly(ethylene irnine) is adsorbed onto the negatively charged surface. In the next step, the adsorbed polyelectrolyte is reacted with a functionalized poly(ethylene oxide) chain. Both reaction steps were followed both by ellipsometry and by direct measurement of surface forces. From these measurements we obtained inforrnation of the adsorbed amount, the layer thickness, as well as the range and distance dependence of the interaction between two PEO-coated surfaces.
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| 37. |
- Claesson, PM, et al.
(författare)
-
Forces between hydrophobic surfaces coated with ethyl(hydroxyethyl)cellulose in the presence of an ionic surfactant
- 1991
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Ingår i: Langmuir. - 0743-7463 .- 1520-5827. ; 7, s. 1441-1446
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Tidskriftsartikel (refereegranskat)abstract
- The forces between hydrophobic surfaces across an aqueous solution containing 0.25% ethyl(hydroxyethyl)cellulose (EHEC) and 4 mM SDS have been studied and compared with the situation in the absence of SDS. A long-range repulsive force (measurable at distances smaller than 1200 Å) is present already after an adsorption time of 30 minutes. The range of the repulsive force increases with time indicating that the adsorption process is rather slow. After 20 hours equilibration, the repulsion was measurable at separations smaller than 2500 Å. The force is rather insensitive to temperature and decays at large separations essentially exponentially, with a decay-length of approximately 300 Å. The force measured on compression is always slightly larger than the one observed on decompression. Hence, the forces are not measured in a true equilibrium situation. The system behaves strikingly different in the absence of SDS (Malmsten and Claesson, Langmuir, in press). Without any surfactant in the EHEC solution less long-range and completely reversible forces are observed. Hence, SDS causes the polymer conformation to be more extended, and is responsible for the non-equilibrium effects observed (e.g. by decreasing the polymer-surface affinity). The adsorbed amount in the presence of SDS was found to be about 1.7 mg/m2 at adsorption equilibrium, independent of temperature (20°-35°C). This is considerably less than in the absence of surfactants (5 mg/m2 at 20°C, 15 mg/m2 at 37°C).
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| 38. |
- Claesson, Per M, et al.
(författare)
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Surfaces coated with ethyl(hydroxyethyl) cellulose : Temperature effects on adsorption and interaction
- 1995
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Ingår i: Cellulose and Cellulose Derivatives. - : Woodhead Publishing Limited. ; , s. 425-433
-
Bokkapitel (refereegranskat)abstract
- The temperature dependence of the forces acting between hydrophobic surfaces coated by a layer of ethyl(hydroxyethyl) cellulose, (EHEC), has been studied as a function of separation and temperature. Both the situation where the adsorbed amount is kept constant and where the adsorbed amount is allowed to vary with temperature have been explored. In both cases the surface interaction is very temperature sensitive due to the temperature dependent interactions between ethylene oxide groups and water. The results are discussed in terms protein repellency of EHEC coated surfaces and in terms of EHEC as a steric stabilizer.
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| 39. |
- Delgado, C, et al.
(författare)
-
Analytical partitioning of poly(ethyleneglycol)-modified proteins
- 1997
-
Ingår i: Journal of chromatography. B. - 1570-0232 .- 1873-376X. ; 692, s. 263-272
-
Tidskriftsartikel (refereegranskat)abstract
- Covalently grafting proteins with varying numbers (n) of poly(ethylene glycol) molecules (PEGs) often enhances their biomedical and industrial usefulness. Partition between the phases in aqueous polymer two-phase systems can be used to rapidly characterize polymer-protein conjugates in a manner related to various enhancements. The logarithm of the partition coefficient (K) approximates linearity over the range 0
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| 40. |
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| 41. |
- Eriksson, J, et al.
(författare)
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Model cellulose films exposed to H. insolens glucoside hydrolase family 45 endo-cellulase—the effect of the carbohydrate-binding module
- 2005
-
Ingår i: Journal of Colloid and Interface Science. - 0021-9797 .- 1095-7103. ; 285, s. 94-99
-
Tidskriftsartikel (refereegranskat)abstract
- The effects of enzyme structure and activity on the degradation of model cellulose substrates were investigated by ellipsometry for the cellulase Humicola insolens GH45. The inactive variant D10N was found to adsorb at the cellulose surface but also to be incorporated into the cellulose films to an extent that depended on pH. For the native protein, the initial adsorption monitored for the inactive variant D10N was followed by enzyme-mediated degradation of the cellulose films. Again, a dependence on pH was found, such that higher pH resulted in slower enzymatic degradation. Removing the carbohydrate-binding module eliminated this pH dependence but also resulted in a decreased adsorption to the cellulose surface, and in a decreased net catalytic effect
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| 42. |
- Griffiths, PC, et al.
(författare)
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Role of copolymer architecture on adsorption at the solid/liquid interface
- 1998
-
Ingår i: Langmuir. - 0743-7463 .- 1520-5827. ; 14, s. 1779-1785
-
Tidskriftsartikel (refereegranskat)abstract
- The adsorption of monodisperse block copolymers comprising poly(ethylene oxide)-poly(butylene oxide) onto polystyrene latex from aqueous solution has been investigated by small-angle neutron scattering and photon correlation spectroscopy with particular reference to the role of molecular architecture. It appears that chain architecture is (i) a weak factor in the adsorption behavior when the hydrophobic block is located in the center of the polymer, since the triblock E100B15E100 behaved very similarly to the cyclic c-E200B15, but (ii) a significant factor when the hydrophobic block is located at the end of the copolymer chain, as shown by the more dense and thicker layer formed by E200B15 compared to the triblock E100B15E100. The hydrodynamic thickness of the layer formed by the small diblock E100B15 was approximately half that exhibited by the larger diblock E200B15. Good agreement was observed between depletion and SANS-derived adsorbed amounts. Theoretical predictions and self-consistent mean-field calculations of the adsorption also show excellent qualitative agreement with experiment.
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| 43. |
- Hahn Berg, IC, et al.
(författare)
-
Ellipsometry and TIRF studies of enzymatic degradation of interfacial proteinaceous layers
- 2001
-
Ingår i: Langmuir. - 0743-7463 .- 1520-5827. ; 17, s. 1641-1652
-
Tidskriftsartikel (refereegranskat)abstract
- Ellipsometry and total internal reflectance fluorescence spectroscopy (TIRF) have been employed to investigate the layer structure of gelatin adsorbed from aqueous solutions onto silica/glass and methylated silica/glass, as well as the effects of addition of the proteolytic enzymes krillase and trypsin, in relation to temperature, enzyme concentration and enzymatic activity. The results for the hydrophilic substrates show that homogeneous and heterogeneous exchange occurs readily, as does autolysis of trypsin at the interface. At the hydrophobic substrates, the effect of exchange is limited and a residual gelatin fraction is present at the interface throughout. The interfacial behavior of gelatin above and below the helix formation temperature (Thelix) shows that more extended surface layers are formed at both substrates below Thelix . At the hydrophilic substrates, the higher adsorbed layer thickness below Thelix is mainly due to the adsorption of more gelatin than at the higher temperature, whereas, at the hydrophobic substrates, the increase in layer thickness below Thelix is due to a decrease in packing density. Enzyme addition to preadsorbed gelatin at methylated silica results in the transition to a thinner and denser layer, that contains both residual gelatin and proteolytic enzymes (i.e., krillase or trypsin). At hydrophobic surfaces, a faster and more extensive degradation of the gelatin layer is observed with increasing krillase concentration, the effect of which is similar above and below Thelix . The effect of trypsin addition to preadsorbed gelatin is enhanced at TThelix . Finally, the exposure of preadsorbed gelatin to inactivated krillase showed a nearly complete elimination in the effects observed upon addition of intact krillase. This indicated that the enzymatic activity of krillase in its native form plays a major role for the interaction between krillase and preadsorbed gelatin.
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| 44. |
- Hahn Berg, IC, et al.
(författare)
-
Proteolytic degradation of oral biofilms in vitro and in vivo: potential of proteases originating from Euphausia superba for plaque control
- 2001
-
Ingår i: European Journal of Oral Sciences. - 0909-8836 .- 1600-0722. ; 109, s. 316-324
-
Tidskriftsartikel (refereegranskat)abstract
- This paper deals with enzymatic removal of dental plaque, in vitro as well as in vivo, using proteases from the Antarctic krill shrimp (Euphausia superba), referred to as Krillase®. Krillase exhibits both endo- and exopeptidase activity but has no microbicidal effect. In model systems with pure cultures of oral microorganisms, Krillase demonstrated inhibition of microbial adhesion to saliva-coated hydroxyapatite. Furthermore, a protocol for the growth of reproducible in vitro plaque films has been developed, and effects of Krillase on the plaque film were investigated by means of scanning electron microscopy (SEM). The results showed that Krillase efficiently released microorganisms from plaque in vitro, the effect being dependent on the enzymatic activity. The surface energy of the substratum had a minor influence on the formation and removal of plaque in vitro. Ellipsometric studies on the formation and enzymatic removal of a salivary pellicle indicated that the enzymatic effect on plaque may partly depend on degradation of the salivary pellicle. Krillase was also able to remove plaque accumulated on dentures in vivo. Our results demonstrate the potential of Krillase for plaque control, and that these enzymes are worthy of further investigations including clinical studies and work to find a suitable vehicle
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| 45. |
- Hahn Berg, IC, et al.
(författare)
-
Salivary protein adsorption onto hydroxyapatite and SDS-mediated elution studied by in situ ellipsometry
- 2001
-
Ingår i: Biofouling (Print). - 0892-7014 .- 1029-2454. ; 17, s. 173-187
-
Tidskriftsartikel (refereegranskat)abstract
- Whole unstimulated saliva from two donors was investigated both with respect to adsorption characteristics and SDS-induced elutability. Salivary protein adsorption onto hydroxyapatite (HA) discs was studied by means of in situ ellipsometry in the concentration range 0.1-20% saliva. The adsorbed amounts on HA were found to be similar to those on silica, but the rates of adsorption were lower. Protein adsorption was virtually unaffected by the presence of Na+, whereas Ca2+ induced nucleation of calcium phosphate at the surface, the deposition rate being influenced by the pellicle age but not by the presence of saliva in bulk solution. The SDS elutability of adsorbed pellicles was determined on HA as well as on silica surfaces. Desorption from both surfaces was found to occur in the same SDS concentration range, although a residual layer was observed on HA. The slight net positive charge and lower charge density of HA as compared to the strongly negatively charged silica, may, at least partly, account for this observation by causing a reduction in the repulsive force between protein-surfactant complexes and the surface. Interindividual differences, observed in the adsorption as well as elution experiments, are thought to relate to the compositional differences observed by SDS-PAGE
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| 46. |
- Hansen, PHF, et al.
(författare)
-
Orthokinetic aggregation in two dimensions of monodisperse and bidisperse colloidal systems
- 1999
-
Ingår i: Journal of Colloid and Interface Science. - 0021-9797 .- 1095-7103. ; 220, s. 269-280
-
Tidskriftsartikel (refereegranskat)abstract
- Orthokinetic aggregation of colloids trapped at the air-liquid interface was studied by direct imaging in a couette cell. This method allowed us to follow the temporal evolution of both the cluster-mass distribution and the cluster structure at a shear rate where Brownian aggregation is suppressed. The interactions between the monodisperse latex particles floating at the air-water interface were controlled either by varying the electrolyte concentration or by creating a bidisperse system through addition of small particles. The results show that the clusters in all the systems are characterized by a high fractal dimension; indicating that the clusters are rearranged and densified by the shear. Kinetic analysis suggests that aggregation of the monodisperse systems mainly proceeds through homogeneous aggregation, i.e. large clusters sticking to other large clusters. The weakly aggregated monodisperse system displayed a transition from heterogeneous to homogenous aggregation of clusters with time which could be related to an incubation time. The bidisperse system, finally, with a size ratio around 10, favored a more heterogeneous aggregation between small and large clusters throughout the aggregation process; a slightly lower fractal dimension was observed compared to the strongly aggregated monodisperse system.
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| 47. |
- Holmberg, K, et al.
(författare)
-
Grafting with hydrophilic polymer chains to prepare protein-resistant surfaces
- 1997
-
Ingår i: Colloids and Surfaces A. - 0927-7757 .- 1873-4359. ; 123-124, s. 297-306
-
Tidskriftsartikel (refereegranskat)abstract
- Different ways of grafting poly(ethylene glycol) (PEG) chains to solid polyethylene were compared with respect to grafting density and efficiency in preventing fibrinogen adsorption. Covalent grafting of PEG was performed by attaching a nucleophilic PEG derivative to electrophilic surface groups or by binding electrophilic PEG to nucleophilic groups at the solid surface. Two adsorption procedures were also used. In the first of these an ethylene oxide - propylene oxide (EO-PO) block copolymer was adsorbed at unmodified, hydrophobic polyethylene. In the second procedure the surface was made carboxyl-functional by free radical grafting of tiglic acid and then exposed to a solution of a positively charged copolymer consisting of PEG chains grafted to poly(ethylene imine) (PEI). According to ESCA measurements, all four routes gave proper PEG grafting densities and the difference in the ratio of C–C–O carbon (from PEG) to C-C-C carbon (from the underlying surface) was relatively small. There was a substantial difference in efficiency in fibrinogen rejection, however. Whereas surface modification with the PEG-PEI graft copolymer gave the lowest, treatment with the EO-PO block copolymer gave the highest amount of protein adsorption. The good effect of the PEG-PEI layer is believed to be related to the large entropy loss associated with protein adsorption on top of this copolymer which is known to be loosely bound in a loops-and-trains configuration. The limited effect of the EO-PO block copolymer may be due to the fact that this polymer is not entirely hydrophilic at the temperature used. Another contributing factor may be that the EO-PO block copolymer, unlike the PEG-PEI graft copolymer, is not irreversibly bound to the surface and may therefore be exchanged by fibrinogen.
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| 48. |
- Jing, Xiaona, et al.
(författare)
-
Interaction of Peptidomimetics with Bilayer Membranes : Biophysical Characterization and Cellular Uptake
- 2012
-
Ingår i: Langmuir. - : American Chemical Society (ACS). - 0743-7463 .- 1520-5827. ; 28:11, s. 5167-5175
-
Tidskriftsartikel (refereegranskat)abstract
- Enzymatically stable cell-penetrating alpha-peptide/beta-peptoid peptidomimetics constitute promising drug delivery vehicles for the transport of therapeutic biomacromolecules across membrane barriers. The aim of the present study was to elucidate the mechanism of peptidomimetic-lipid bilayer interactions. A series of peptidomimetics consisting of alternating cationic and hydrophobic residues displaying variation in length and N-terminal end group were applied to fluid-phase, anionic lipid bilayers, and their interaction was investigated using isothermal titration calorimetry (ITC) and ellipsometry. Titration of lipid vesicles into solutions of peptidomimetics resulted in exothermic adsorption processes, and the interaction of all studied peptidomimetics with anionic lipid membranes was found to be enthalpy-driven. The enthalpy and Gibbs free energy (Delta G) proved more favorable with increasing chain length. However, not all charges contribute equally to the interaction, as evidenced by the charge-normalized Delta G being inversely correlated to the sequence length. Ellipsometry data suggested that the hydrophobic residues also played an important role in the interaction process. Furthermore, Delta G extracted from ellipsometry data showed good agreement with that obtained with ITC. To further elucidate their interaction with biological membranes, quantitative uptake and cellular distribution were studied in proliferating HeLa cells by flow cytometry and confocal microscopy. The cellular uptake of carboxyfluorescein-labeled peptidomimetics showed a similar ranking as that obtained from the adsorbed amount, and binding energy to model membranes demonstrated that the initial interaction with the membrane is of key importance for the cellular uptake.
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| 49. |
- Jing, Xiaona, et al.
(författare)
-
Membrane adsorption and binding, cellular uptake and cytotoxicity of cell-penetrating peptidomimetics with alpha-peptide/beta-peptoid backbone : Effects of hydrogen bonding and alpha-chirality in the beta-peptoid residues
- 2012
-
Ingår i: Biochimica et Biophysica Acta - Biomembranes. - : Elsevier BV. - 0005-2736 .- 1879-2642. ; 1818:11, s. 2660-2668
-
Tidskriftsartikel (refereegranskat)abstract
- Cell-penetrating peptides (CPPs) provide a promising approach for enhancing intracellular delivery of therapeutic biomacromolecules by increasing transport through membrane barriers. Here, proteolytically stable cell-penetrating peptidomimetics with alpha-peptide/beta-peptoid backbone were studied to evaluate the effect of alpha-chirality in the beta-peptoid residues and the presence of guanidinium groups in the alpha-amino acid residues on membrane interaction. The molecular properties of the peptidomimetics in solution (surface and intramolecular hydrogen bonding, aqueous diffusion rate and molecular size) were studied along with their adsorption to lipid bilayers, cellular uptake, and toxicity. The surface hydrogen bonding ability of the peptidomimetics reflected their adsorbed amounts onto lipid bilayers as well as with their cellular uptake, indicating the importance of hydrogen bonding for their membrane interaction and cellular uptake. Ellipsometry studies further demonstrated that the presence of chiral centers in the beta-peptoid residues promotes a higher adsorption to anionic lipid bilayers, whereas circular dichroism results showed that alpha-chirality influences their overall mean residue ellipticity. The presence of guanidinium groups and alpha-chiral beta-peptoid residues was also found to have a significant positive effect on uptake in living cells. Together, the findings provide an improved understanding on the behavior of cell-penetrating peptidomimetics in the presence of lipid bilayers and live cells.
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| 50. |
- Joiner, A, et al.
(författare)
-
Adsorption from black tea and red wine onto in vitro salivary pellicles studied by ellipsometry
- 2003
-
Ingår i: European Journal of Oral Sciences. - : Blackwell Munksgaard. - 0909-8836 .- 1600-0722. ; 111, s. 417-422
-
Tidskriftsartikel (refereegranskat)abstract
- The adsorption of black tea and red wine components onto a pellicle-like protein layer formed in vitro by adsorption from whole unstimulated saliva on hydroxyapatite discs were studied by in situ ellipsometry. It was found that components from black tea readily adsorbed to the pellicle. Subsequent exposure to saliva led to further adsorption of salivary components to give an overall increase in the amounts adsorbed. The amounts adsorbed increased still further following a third tea and saliva exposure. Components of red wine gave significantly greater amounts of adsorption to the pellicle than black tea. The adsorption of components of black tea gave a concomitant increase in colour or stain as measured by a reflectance chromameter. In all cases, the black tea- and red wine-modified pellicles were not eluted by either phosphate buffer or sodium dodecyl sulphate (SDS) rinses. Thus, black tea and red wine components have been shown to have a profound effect on in vitro pellicle maturation, causing thickened layers of stained material to build up, which are not readily removed.
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