| 1. |
- Gross, Sean M., et al.
(author)
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A multi-omic analysis of MCF10A cells provides a resource for integrative assessment of ligand-mediated molecular and phenotypic responses
- 2022
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In: Communications Biology. - : Springer Nature. - 2399-3642. ; 5:1
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Journal article (peer-reviewed)abstract
- The phenotype of a cell and its underlying molecular state is strongly influenced by extracellular signals, including growth factors, hormones, and extracellular matrix proteins. While these signals are normally tightly controlled, their dysregulation leads to phenotypic and molecular states associated with diverse diseases. To develop a detailed understanding of the linkage between molecular and phenotypic changes, we generated a comprehensive dataset that catalogs the transcriptional, proteomic, epigenomic and phenotypic responses of MCF10A mammary epithelial cells after exposure to the ligands EGF, HGF, OSM, IFNG, TGFB and BMP2. Systematic assessment of the molecular and cellular phenotypes induced by these ligands comprise the LINCS Microenvironment (ME) perturbation dataset, which has been curated and made publicly available for community-wide analysis and development of novel computational methods ( synapse.org/LINCS_MCF10A ). In illustrative analyses, we demonstrate how this dataset can be used to discover functionally related molecular features linked to specific cellular phenotypes. Beyond these analyses, this dataset will serve as a resource for the broader scientific community to mine for biological insights, to compare signals carried across distinct molecular modalities, and to develop new computational methods for integrative data analysis.
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| 2. |
- Feiler, Adam A., et al.
(author)
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Adsorption and viscoelastic properties of fractionated mucin (BSM) and bovine serum albumin (BSA) studied with quartz crystal microbalance (QCM-D)
- 2007
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In: Journal of Colloid and Interface Science. - : Elsevier BV. - 0021-9797 .- 1095-7103. ; 315:2, s. 475-481
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Journal article (peer-reviewed)abstract
- The adsorption profile and viscoelastic properties of bovine submaxillary gland mucin (BSM) and bovine serum albumin (BSA), extracted from a commercial mucin preparation, adsorbing to polystyrene surfaces has been studied using quartz crystal microbalance with dissipation monitoring (QCM-D). A significant difference in the adsorption properties of the different proteins was detected; with the BSA adsorbing in a flat rigid layer whilst the mucin adsorbed in a diffuse, highly viscoelastic layer. Subsequent addition of BSA to the preadsorbed mucin layer resulted in stiffening of the protein layer which was attributed to complexation of the mucin by BSA. In contrast, a preadsorbed layer of BSA prevented mucin adsorption altogether. Combined mixtures of mucin and BSA in well defined ratios revealed intermediate properties between the two separate protein species which varied systematically with the protein ratios. The results shed light on the synergistic effects of complexation of lower molecular weight biomolecular species with mucin. The possibility to selectively control protein uptake and tailor the physical properties of the adsorbed layer makes mucin an attractive option for application in biomaterial coatings.
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| 3. |
- Feiler, Adam A., et al.
(author)
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Adsorption of anionic gold nanoparticles by a layer of cationic microgel particles deposited on a gold-coated, quartz surface : studied by quartz crystal microbalance and atomic force microscopy
- 2011
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In: Soft Matter. - : Royal Society of Chemistry (RSC). - 1744-683X .- 1744-6848. ; 7:14, s. 6660-6670
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Journal article (peer-reviewed)abstract
- The uptake of gold [Au-MES] nanoparticles by pH-responsive poly(2-vinylpyridine) [P2VP] microgel particles, deposited on a surface, has been studied using a quartz crystal microbalance with dissipation monitoring [QCM-D]. QCM-D, which has not previously been applied to such systems, has been shown to be a promising technique for their analysis, especially when combined with a complementary technique such as atomic force microscopy [AFM]. The QCM-D technique, which provides information on mass and viscosity changes of material adsorbed to a surface, has been used to follow the adsorption of microgel particles to a surface, their subsequent swelling and collapse due to changing the system pH, and the uptake of Au-MES nanoparticles by the P2VP particles. Microgel particles with differing cross-linker content have been compared, following uptake by microgel particles in both their collapsed and swollen states. Qualitative differences in the QCM-D response were observed between microgels with differing cross-linker content (and hence different swelling properties). It was shown that uptake of Au-MES nanoparticles acted to fully and irreversibly collapse the swollen P2VP microgels, inhibiting their pH response. The Sauerbrey relationship was used to equate frequency changes measured by QCM-D to mass allowing sorption amounts for the uptake of Au-MES nanoparticles by P2VP particles to be obtained for these surface-constrained systems.
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| 4. |
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| 5. |
- Leyton-Jaimes, M. F., et al.
(author)
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Empty mesoporous silica particles significantly delay disease progression and extend survival in a mouse model of ALS
- 2020
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In: Scientific Reports. - : Nature Research. - 2045-2322. ; 10:1
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Journal article (peer-reviewed)abstract
- Amyotrophic lateral sclerosis (ALS) is a devastating incurable neurological disorder characterized by motor neuron (MN) death and muscle dysfunction leading to mean survival time after diagnosis of only 2–5 years. A potential ALS treatment is to delay the loss of MNs and disease progression by the delivery of trophic factors. Previously, we demonstrated that implanted mesoporous silica nanoparticles (MSPs) loaded with trophic factor peptide mimetics support survival and induce differentiation of co-implanted embryonic stem cell (ESC)-derived MNs. Here, we investigate whether MSP loaded with peptide mimetics of ciliary neurotrophic factor (Cintrofin), glial-derived neurotrophic factor (Gliafin), and vascular endothelial growth factor (Vefin1) injected into the cervical spinal cord of mutant SOD1 mice affect disease progression and extend survival. We also transplanted boundary cap neural crest stem cells (bNCSCs) which have been shown previously to have a positive effect on MN survival in vitro and in vivo. We show that mimetic-loaded MSPs and bNCSCs significantly delay disease progression and increase survival of mutant SOD1 mice, and also that empty particles significantly improve the condition of ALS mice. Our results suggest that intraspinal delivery of MSPs is a potential therapeutic approach for the treatment of ALS.
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| 6. |
- Valle-Delgado, J. J., et al.
(author)
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Hydration forces between silica surfaces : Experimental data and predictions from different theories
- 2005
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In: Journal of Chemical Physics. - : AIP Publishing. - 0021-9606 .- 1089-7690. ; 123, s. 034708-
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Journal article (peer-reviewed)abstract
- Silica is a very interesting system that has been thoroughly studied in the last decades. One of the most outstanding characteristics of silica suspensions is their stability in solutions at high salt concentrations. In addition to that, measurements of direct-interaction forces between silica surfaces, obtained by different authors by means of surface force apparatus or atomic force microscope (AFM), reveal the existence of a strong repulsive interaction at short distances (below 2 nm) that decays exponentially. These results cannot be explained in terms of the classical Derjaguin, Landau, Verwey, and Overbeek (DLVO) theory, which only considers two types of forces: the electrical double-layer repulsion and the London-van der Waals attraction. Although there is a controversy about the origin of the short-range repulsive force, the existence of a structured layer of water molecules at the silica surface is the most accepted explanation for it. The overlap of structured water layers of different surfaces leads to repulsive forces, which are known as hydration forces. This assumption is based on the very hydrophilic nature of silica. Different theories have been developed in order to reproduce the exponentially decaying behavior (as a function of the separation distance) of the hydration forces. Different mechanisms for the formation of the structured water layer around the silica surfaces are considered by each theory. By the aid of an AFM and the colloid probe technique, the interaction forces between silica surfaces have been measured directly at different pH values and salt concentrations. The results confirm the presence of the short-range repulsion at any experimental condition (even at high salt concentration). A comparison between the experimental data and theoretical fits obtained from different theories has been performed in order to elucidate the nature of this non-DLVO repulsive force.
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| 7. |
- Valle-Delgado, J. J., et al.
(author)
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Interaction forces between BSA layers adsorbed on silica surfaces measured with an atomic force microscope
- 2004
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In: Journal of Physical Chemistry B. - : American Chemical Society (ACS). - 1520-6106 .- 1520-5207. ; 108:17, s. 5365-5371
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Journal article (peer-reviewed)abstract
- The interaction forces between bovine serum albumin (BSA) layers adsorbed on silica surfaces have been measured using an atomic force microscope (AFM) in Conjunction with the colloid probe technique. Measurements of force-distance curves were made at different pH values and electrolyte concentrations (NaCl and CaCl2). The interaction at long range is dominated by electrical double-layer forces, while at short surface separations an additional repulsion due to the compression of the adsorbed protein layers appears. However, prior to this steric interaction, when the pH is above the isoelectric point of the protein and at high salt concentration, a non-DLVO repulsive interaction is observed. This behavior is explained if the presence of hydration forces in the system is assumed. Theoretical predictions including a hydration term in the DLVO theory fit the experimental results satisfactorily. The results presented in this article provide a direct confirmation that the AFM colloid probe technique can provide a useful way of directly quantifying the interaction of biological macromolecules.
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| 8. |
- Valle-Delgado, J. J., et al.
(author)
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Interactions between bovine serum albumin layers adsorbed on different substrates measured with an atomic force microscope
- 2004
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In: Physical Chemistry, Chemical Physics - PCCP. - : Royal Society of Chemistry (RSC). - 1463-9076 .- 1463-9084. ; 6:7, s. 1482-1486
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Journal article (peer-reviewed)abstract
- By the aid of an atomic force microscope (AFM) and the colloid probe technique, the interaction forces between bovine serum albumin (BSA) layers adsorbed on different substrates (silica and polystyrene) have been measured directly as a function of pH and salt concentration. Electrostatic and steric forces dominate the interactions at low salt concentrations. At high salt concentrations, when electrostatic interactions are screened, a very strange behaviour is found as a function of pH. The behaviour around the i.e.p. of the protein is also very striking: the interaction is attractive at low salt concentration, but it is repulsive at high salt concentration. These results could be explained if the presence of hydration forces is assumed. Theoretical predictions including a hydration term in the DLVO theory fit the experimental results satisfactorily.
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| 9. |
- Valle-Delgado, J. J., et al.
(author)
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Measurement of interactions between protein layers adsorbed on silica by atomic force microscopy
- 2004
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In: Journal of Physics. - : IOP Publishing. - 0953-8984 .- 1361-648X. ; 16:26, s. 2383-2392
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Journal article (peer-reviewed)abstract
- The present work, using an atomic force microscope and the colloid probe technique, investigates the interaction forces between bovine serum albumin (BSA) layers and between apoferritin layers adsorbed on silica surfaces. The measurements have been carried out in an aqueous medium at different pH values and NaCl concentrations. Similar behaviours have been found with both proteins. Electrostatic and steric forces dominate the interactions between the protein layers at low NaCl concentrations. However, a very strange behaviour is found as a function of pH at high NaCl concentrations. The results obtained under these conditions could be explained if the presence of hydration forces in these systems is assumed.
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| 10. |
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