| 1. |
- Sepehri, Sobhan, 1986, et al.
(författare)
-
Characterization of Binding of Magnetic Nanoparticles to Rolling Circle Amplification Products by Turn-On Magnetic Assay
- 2019
-
Ingår i: Biosensors-Basel. - : MDPI AG. ; 9:3
-
Tidskriftsartikel (refereegranskat)abstract
- The specific binding of oligonucleotide-tagged 100 nm magnetic nanoparticles (MNPs) to rolling circle products (RCPs) is investigated using our newly developed differential homogenous magnetic assay (DHMA). The DHMA measures ac magnetic susceptibility from a test and a control samples simultaneously and eliminates magnetic background signal. Therefore, the DHMA can reveal details of binding kinetics of magnetic nanoparticles at very low concentrations of RCPs. From the analysis of the imaginary part of the DHMA signal, we find that smaller MNPs in the particle ensemble bind first to the RCPs. When the RCP concentration increases, we observe the formation of agglomerates, which leads to lower number of MNPs per RCP at higher concentrations of RCPs. The results thus indicate that a full frequency range of ac susceptibility observation is necessary to detect low concentrations of target RCPs and a long amplification time is not required as it does not significantly increase the number of MNPs per RCP. The findings are critical for understanding the underlying microscopic binding process for improving the assay performance. They furthermore suggest DHMA is a powerful technique for dynamically characterizing the binding interactions between MNPs and biomolecules in fluid volumes.
|
|
| 2. |
- Brandt, Erik G., et al.
(författare)
-
Molecular dynamics study of zinc binding to cysteines in a peptide mimic of the alcohol dehydrogenase structural zinc site
- 2009
-
Ingår i: Physical Chemistry, Chemical Physics - PCCP. - : Royal Society of Chemistry (RSC). - 1463-9076 .- 1463-9084. ; 11:6, s. 975-983
-
Tidskriftsartikel (refereegranskat)abstract
- The binding of zinc (Zn) ions to proteins is important for many cellular events. The theoretical and computational description of this binding (as well as that of other transition metals) is a challenging task. In this paper the binding of the Zn ion to four cysteine residues in the structural site of horse liver alcohol dehydrogenase (HLADH) is studied using a synthetic peptide mimic of this site. The study includes experimental measurements of binding constants, classical free energy calculations from molecular dynamics (MD) simulations and quantum mechanical (QM) electron structure calculations. The classical MD results account for interactions at the molecular level and reproduce the absolute binding energy and the hydration free energy of the Zn ion with an accuracy of about 10%. This is insufficient to obtain correct free energy differences. QM correction terms were calculated from density functional theory (DFT) on small clusters of atoms to include electronic polarisation of the closest waters and covalent contributions to the Zn-S coordination bond. This results in reasonably good agreement with the experimentally measured binding constants and Zn ion hydration free energies in agreement with published experimental values. The study also includes the replacement of one cysteine residue to an alanine. Simulations as well as experiments showed only a small effect of this upon the binding free energy. A detailed analysis indicate that the sulfur is replaced by three water molecules, thereby changing the coordination number of Zn from four (as in the original peptide) to six (as in water).
|
|
| 3. |
- Cronholm, Pontus, et al.
(författare)
-
Intracellular Uptake and Toxicity of Ag and CuO Nanoparticles : A Comparison Between Nanoparticles and their Corresponding Metal Ions
- 2013
-
Ingår i: Small. - : Wiley. - 1613-6810 .- 1613-6829. ; 9:7, s. 970-982
-
Tidskriftsartikel (refereegranskat)abstract
- An increased understanding of nanoparticle toxicity and its impact on human health is essential to enable a safe use of nanoparticles in our society. The aim of this study is to investigate the role of a Trojan horse type mechanism for the toxicity of Ag-nano and CuO-nano particles and their corresponding metal ionic species (using CuCl2 and AgNO3), i.e., the importance of the solid particle to mediate cellular uptake and subsequent release of toxic species inside the cell. The human lung cell lines A549 and BEAS-2B are used and cell death/membrane integrity and DNA damage are investigated by means of trypan blue staining and the comet assay, respectively. Chemical analysis of the cellular dose of copper and silver is performed using atomic absorption spectroscopy. Furthermore, transmission electron microscopy, laser scanning confocal microscopy, and confocal Raman microscopy are employed to study cellular uptake and particle-cell interactions. The results confirm a high uptake of CuO-nano and Ag-nano compared to no, or low, uptake of the soluble salts. CuO-nano induces both cell death and DNA damage whereas CuCl2 induces no toxicity. The opposite is observed for silver, where Ag-nano does not cause any toxicity, whereas AgNO3 induces a high level of cell death. In conclusion: CuO-nano toxicity is predominantly mediated by intracellular uptake and subsequent release of copper ions, whereas no toxicity is observed for Ag-nano due to low release of silver ions within short time periods.
|
|
| 4. |
- Gazzi, Arianna, et al.
(författare)
-
Graphene, other carbon nanomaterials and the immune system: toward nanoimmunity-by-design
- 2020
-
Ingår i: JPhys Materials. - : IOP Publishing. - 2515-7639. ; 3:3
-
Tidskriftsartikel (refereegranskat)abstract
- Carbon-based materials (CBMs), such as graphene, nanodiamonds, carbon fibers, and carbon dots, have attracted a great deal scientific attention due to their potential as biomedical tools. Following exposure, particularly intravenous injection, these nanomaterials can be recognized by immune cells. Such interactions could be modulated by the different physicochemical properties of the materials (e.g. structure, size, and chemical functions), by either stimulating or suppressing the immune response. However, a harmonized cutting-edge approach for the classification of these materials based not only on their physicochemical parameters but also their immune properties has been missing. The European Commission-funded G-IMMUNOMICS and CARBO-IMmap projects aimed to fill this gap, developing a functional pipeline for the qualitative and quantitative immune characterization of graphene, graphene-related materials (GRMs), and other CBMs. The goal was to open breakthrough perspectives for the definition of the immune profiles of these materials. Here, we summarize our methodological approach, key results, and the necessary multidisciplinary expertise ranging across various fields, from material chemistry to engineering, immunology, toxicology, and systems biology. G-IMMUNOMICS, as a partnering project of the Graphene Flagship, the largest scientific research initiative on graphene worldwide, also complemented the studies performed in the Flagship on health and environmental impact of GRMs. Finally, we present the nanoimmunity-by-design concept, developed within the projects, which can be readily applied to other 2D materials. Overall, the G-IMMUNOMICS and CARBO-IMmap projects have provided new insights on the immune impact of GRMs and CBMs, thus laying the foundation for their safe use and future translation in medicine.
|
|
| 5. |
- Granskog, Viktor, et al.
(författare)
-
Linear Dendritic Block Copolymers as Promising Biomaterials for the Manufacturing of Soft Tissue Adhesive Patches Using Visible Light Initiated Thiol-Ene Coupling Chemistry
- 2015
-
Ingår i: Advanced Functional Materials. - : Wiley-VCH Verlagsgesellschaft. - 1616-301X .- 1616-3028. ; 25:42, s. 6596-6605
-
Tidskriftsartikel (refereegranskat)abstract
- A library of dendritic-linear-dendritic (DLD) materials comprising linear poly(ethylene glycol) and hyperbranched dendritic blocks based on 2,2-bis(hydroxymethyl) propionic acid is successfully synthesized and post-functionalized with peripheral allyl groups. Reactive DLDs with pseudo-generations of 3 to 6 (G3-G6) are isolated in large scale allowing their thorough evaluation as important components for the development of biomedical adhesives. Due to their branched nature and inherent degradable ester-bonds, promising biomaterial resins are accomplished with suitable viscosity, eliminating the excessive use of co-solvents. By utilizing benign high-energy visible light initiated thiol-ene coupling chemistry, DLDs together with tris[2-(3-mercaptopropionyloxy) ethyl] isocyanurate and surgical mesh enable the fabrication of soft tissue adhesive patches (STAPs) within a total irradiation time of 30 s. The STAPs display the ability to create good adhesion to wet soft tissue and encouraging results in cytotoxicity tests. All crosslinked materials are also found to degrade after being stored in human blood plasma and phosphate buffered saline. The proposed benign methodology coupled with the promising features of the crosslinked materials is herein envisioned as a soft tissue adhesive with properties that do not exist in currently available tissue adhesives.
|
|
| 6. |
- Kowalewski, Jacob M, et al.
(författare)
-
Modeling the impact of store-operated Ca2+ entry on intracellular Ca2+ oscillations
- 2006
-
Ingår i: Mathematical biosciences. - : Elsevier BV. - 0025-5564. ; 204:2, s. 232-249
-
Tidskriftsartikel (refereegranskat)abstract
- Calcium (Ca2+) oscillations play fundamental roles in various cell signaling processes and have been the subject of numerous modeling studies. Here we have implemented a general mathematical model to simulate the impact of store-operated Ca2+ entry on intracellular Ca2+ oscillations. In addition, we have compared two different models of the inositol 1,4,5-trisphosphate (IP3) receptor (IP3R) and their influences on intracellular Ca2+ oscillations. Store-operated Ca2+ entry following Ca2+ depletion of endoplasmic reticulum (ER) is an important component of Ca2+ signaling. We have developed a phenomenological model of store-operated Ca2+ entry via store-operated Ca2+ (SOC) channels, which are activated upon ER Ca2+ depletion. The depletion evokes a bi-phasic Ca2+ signal, which is also produced in our mathematical model. The IP3R is an important regulator of intracellular Ca2+ signals. This IP3 sensitive Ca2+ channel is also regulated by Ca2+. We apply two IP3R models, the Mak-McBride-Foskett model and the De Young and Keizer model, with significantly different channel characteristics. Our results show that the two separate IP3R models evoke intracellular Ca2+ oscillations with different frequencies and amplitudes. Store-operated Ca2+ entry affects the oscillatory behavior of these intracellular Ca2+ oscillations. The IP3 threshold is altered when store-operated Ca2+ entry is excluded from the model. Frequencies and amplitudes of intracellular Ca2+ oscillations are also altered without store-operated Ca2+ entry. Under certain conditions, when intracellular Ca2+ oscillations are absent, excluding store-operated Ca2+ entry induces an oscillatory response. These findings increase knowledge concerning store-operated Ca2+ entry and its impact on intracellular Ca2+ oscillations.
|
|
| 7. |
- Li, Juan, et al.
(författare)
-
Ouabain protects against adverse developmental programming of the kidney
- 2010
-
Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 1, s. 42-
-
Tidskriftsartikel (refereegranskat)abstract
- The kidney is extraordinarily sensitive to adverse fetal programming. Malnutrition, the most common form of developmental challenge, retards the formation of functional units, the nephrons. The resulting low nephron endowment increases susceptibility to renal injury and disease. Using explanted rat embryonic kidneys, we found that ouabain, the Na, K-ATPase ligand, triggers a calcium-nuclear factor-kappa B signal, which protects kidney development from adverse effects of malnutrition. To mimic malnutrition, kidneys were serum deprived for 24 h. This resulted in severe retardation of nephron formation and a robust increase in apoptosis. In ouabain-exposed kidneys, no adverse effects of serum deprivation were observed. Proof of principle that ouabain rescues development of embryonic kidneys exposed to malnutrition was obtained from studies on pregnant rats given a low-protein diet and treated with ouabain or vehicle throughout pregnancy. Thus, we have identified a survival signal and a feasible therapeutic tool to prevent adverse programming of kidney development.
|
|
| 8. |
- Manneberg, Otto, et al.
(författare)
-
A three-dimensional ultrasonic cage for characterization of individual cells
- 2008
-
Ingår i: Applied Physics Letters. - : AIP Publishing. - 0003-6951 .- 1077-3118. ; 93, s. 063901-
-
Tidskriftsartikel (refereegranskat)abstract
- We demonstrate enrichment, controlled aggregation, and manipulation of microparticles and cells by an ultrasonic cage integrated in a microfluidic chip compatible with high-resolution optical microscopy. The cage is designed as a dual-frequency resonant filleted square box integrated in the fluid channel. Individual particles may be trapped three dimensionally, and the dimensionality of one-dimensional to three-dimensional aggregates can be controlled. We investigate the dependence of the shape and position of a microparticle aggregate on the actuation voltages and aggregate size, and demonstrate optical monitoring of individually trapped live cells with submicrometer resolution.
|
|
| 9. |
- McCuskey, Samantha R., et al.
(författare)
-
Current Progress of Interfacing Organic Semiconducting Materials with Bacteria
- 2022
-
Ingår i: Chemical Reviews. - : American Chemical Society (ACS). - 0009-2665 .- 1520-6890. ; 122:4, s. 4791-4825
-
Forskningsöversikt (refereegranskat)abstract
- Microbial bioelectronics require interfacing microorganisms with electrodes. The resulting abiotic/biotic platforms provide the basis of a range of technologies, including energy conversion and diagnostic assays. Organic semiconductors (OSCs) provide a unique strategy to modulate the interfaces between microbial systems and external electrodes, thereby improving the performance of these incipient technologies. In this review, we explore recent progress in the field on how OSCs, and related materials capable of charge transport, are being used within the context of microbial systems, and more specifically bacteria. We begin by examining the electrochemical communication modes in bacteria and the biological basis for charge transport. Different types of synthetic organic materials that have been designed and synthesized for interfacing and interrogating bacteria are discussed next, followed by the most commonly used characterization techniques for evaluating transport in microbial, synthetic, and hybrid systems. A range of applications is subsequently examined, including biological sensors and energy conversion systems. The review concludes by summarizing what has been accomplished so far and suggests future design approaches for OSC bioelectronics materials and technologies that hybridize characteristic properties of microbial and OSC systems.
|
|
| 10. |
- Padinhare, Harikesh, et al.
(författare)
-
Ion-tunable antiambipolarity in mixed ion-electron conducting polymers enables biorealistic organic electrochemical neurons
- 2023
-
Ingår i: Nature Materials. - : NATURE PORTFOLIO. - 1476-1122 .- 1476-4660. ; 22, s. 242-248
-
Tidskriftsartikel (refereegranskat)abstract
- Biointegrated neuromorphic hardware holds promise for new protocols to record/regulate signalling in biological systems. Making such artificial neural circuits successful requires minimal device/circuit complexity and ion-based operating mechanisms akin to those found in biology. Artificial spiking neurons, based on silicon-based complementary metal-oxide semiconductors or negative differential resistance device circuits, can emulate several neural features but are complicated to fabricate, not biocompatible and lack ion-/chemical-based modulation features. Here we report a biorealistic conductance-based organic electrochemical neuron (c-OECN) using a mixed ion-electron conducting ladder-type polymer with stable ion-tunable antiambipolarity. The latter is used to emulate the activation/inactivation of sodium channels and delayed activation of potassium channels of biological neurons. These c-OECNs can spike at bioplausible frequencies nearing 100 Hz, emulate most critical biological neural features, demonstrate stochastic spiking and enable neurotransmitter-/amino acid-/ion-based spiking modulation, which is then used to stimulate biological nerves in vivo. These combined features are impossible to achieve using previous technologies.
|
|
