Virginia Brizuela | FCEFyN, UNC (original) (raw)
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Papers by Virginia Brizuela
Soft Matter, 2010
A family of polymer substrates which consists of a vinyl backbone chain with the side groups -COO... more A family of polymer substrates which consists of a vinyl backbone chain with the side groups -COO(CH 2 ) x CH 3 , with x ¼ 0, 1, 3, 5 was prepared. Substrates with decreasing stiffness, characterised by the elastic modulus at 37 C, and similar chemical groups were obtained. Firstly, we have investigated whether these minute variations in polymer chemistry lead to differences in fibronectin (FN) adsorption: the same FN density was obtained on every substrate (450 ng cm À2 ) but the supramolecular organisation of the protein at the material interface, as obtained with AFM, was different for x ¼ 0 and the other surfaces (x ¼ 1, 3, 5). Consequently, this allows one to use a set of substrates (x ¼ 1, 3, 5) to investigate the effect of substrate stiffness on cell behavior as the unique physical parameter, i.e. after ruling out any influence of the length of the side group on protein conformation. Moreover, the importance of investigating the intermediate layer of proteins at the cellmaterial interface is stressed: the effect of x ¼ 0 and x ¼ 1 on cell behavior cannot be ascribed to the different stiffness of the substrate anymore, since the biological activity of the protein on the material surface was also different. Afterwards, initial cellular interaction was investigated using MC3T3-E1 osteoblasts-like cells and focusing on actin cytoskeleton development, focal adhesion formation and the ability of cells to reorganize the adsorbed FN layer on the different substrates. Image analysis was used to quantify the frequency distribution of the focal plaques, which revealed broader distributions on the stiffer substrates, with formation of larger focal plaques revealing that cells exert higher forces on stiffer substrates.
Molecular Pharmacology, 2007
We examined the role of sphingosine kinase-1 (SphK1), a critical regulator of the ceramide/sphing... more We examined the role of sphingosine kinase-1 (SphK1), a critical regulator of the ceramide/sphingosine 1-phosphate (S1P) biostat, in the regulation of death and survival of SH-SY5Y neuroblastoma cells in response to amyloid  (A) peptide (25-35). Upon incubation with A, SH-SY5Y cells displayed a marked down-regulation of SphK1 activity coupled with an increase in the ceramide/S1P ratio followed by cell death. This mechanism was redox-sensitive; N-acetylcysteine totally abrogated the down-regulation of SphK1 activity and strongly inhibited A-induced cell death. SphK1 overexpression impaired the cytotoxicity of A, whereas SphK1 silencing by RNA interference mimicked A-induced cell death, thereby establishing Supported by the Institut National de la Santé et de la Recherche Médicale, the Centre National de la Recherche Scientifique, and Groupement d'Intérêt Scientifique 'Infections à Prions.'
Volumen de mezclado Objetivo:
Soft Matter, 2010
A family of polymer substrates which consists of a vinyl backbone chain with the side groups -COO... more A family of polymer substrates which consists of a vinyl backbone chain with the side groups -COO(CH 2 ) x CH 3 , with x ¼ 0, 1, 3, 5 was prepared. Substrates with decreasing stiffness, characterised by the elastic modulus at 37 C, and similar chemical groups were obtained. Firstly, we have investigated whether these minute variations in polymer chemistry lead to differences in fibronectin (FN) adsorption: the same FN density was obtained on every substrate (450 ng cm À2 ) but the supramolecular organisation of the protein at the material interface, as obtained with AFM, was different for x ¼ 0 and the other surfaces (x ¼ 1, 3, 5). Consequently, this allows one to use a set of substrates (x ¼ 1, 3, 5) to investigate the effect of substrate stiffness on cell behavior as the unique physical parameter, i.e. after ruling out any influence of the length of the side group on protein conformation. Moreover, the importance of investigating the intermediate layer of proteins at the cellmaterial interface is stressed: the effect of x ¼ 0 and x ¼ 1 on cell behavior cannot be ascribed to the different stiffness of the substrate anymore, since the biological activity of the protein on the material surface was also different. Afterwards, initial cellular interaction was investigated using MC3T3-E1 osteoblasts-like cells and focusing on actin cytoskeleton development, focal adhesion formation and the ability of cells to reorganize the adsorbed FN layer on the different substrates. Image analysis was used to quantify the frequency distribution of the focal plaques, which revealed broader distributions on the stiffer substrates, with formation of larger focal plaques revealing that cells exert higher forces on stiffer substrates.
Molecular Pharmacology, 2007
We examined the role of sphingosine kinase-1 (SphK1), a critical regulator of the ceramide/sphing... more We examined the role of sphingosine kinase-1 (SphK1), a critical regulator of the ceramide/sphingosine 1-phosphate (S1P) biostat, in the regulation of death and survival of SH-SY5Y neuroblastoma cells in response to amyloid  (A) peptide (25-35). Upon incubation with A, SH-SY5Y cells displayed a marked down-regulation of SphK1 activity coupled with an increase in the ceramide/S1P ratio followed by cell death. This mechanism was redox-sensitive; N-acetylcysteine totally abrogated the down-regulation of SphK1 activity and strongly inhibited A-induced cell death. SphK1 overexpression impaired the cytotoxicity of A, whereas SphK1 silencing by RNA interference mimicked A-induced cell death, thereby establishing Supported by the Institut National de la Santé et de la Recherche Médicale, the Centre National de la Recherche Scientifique, and Groupement d'Intérêt Scientifique 'Infections à Prions.'
Volumen de mezclado Objetivo: