Shamik Sen | Indian Institute of Technology Bombay (original) (raw)
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SRI RAM MURTI SMARAK COLLEGE OF ENGG. 7TECHNOLOGY(BAREILLY)U.P
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Papers by Shamik Sen
Biophysical Journal, 2010
Glioblastoma Multiforme (GBM) is a malignant astrocytic tumor associated with low survival rates ... more Glioblastoma Multiforme (GBM) is a malignant astrocytic tumor associated with low survival rates because of aggressive infiltration of tumor cells into the brain parenchyma. Expression of the actin binding protein a-actinin has been strongly correlated with the invasive phenotype of GBM in vivo. To probe the cellular basis of this correlation, we have suppressed expression of the nonmuscle isoforms a-actinin-1 and a-actinin-4 and examined the contribution of each isoform to the structure, mechanics, and motility of human glioma tumor cells in culture. While subcellular localization of each isoform is distinct, suppression of either isoform yields a phenotype that includes dramatically reduced motility, compensatory upregulation and redistribution of vinculin, reduced cortical elasticity, and reduced ability to adapt to changes in the elasticity of the extracellular matrix (ECM). Mechanistic studies reveal a relationship between a-actinin and non-muscle myosin II in which depletion of either a-actinin isoform reduces myosin expression and maximal cell-ECM tractional forces. Our results demonstrate that both a-actinin-1 and a-actinin-4 make critical and distinct contributions to cytoskeletal organization, rigidity-sensing, and motility of glioma cells, thereby yielding mechanistic insight into the observed correlation between a-actinin expression and GBM invasiveness in vivo.
International journal of cell biology, 2012
The extracellular matrix (ECM) is known to provide various physicochemical cues in directing cell... more The extracellular matrix (ECM) is known to provide various physicochemical cues in directing cell behavior including composition, topography, and dimensionality. Physical remodeling of the ECM has been documented in a variety of cancers. In breast cancer, the increased deposition of matrix proteins, their crosslinking, and alignment create a stiffer microenvironment that activates cell contractility and promotes cancer invasion. In this paper, we sought to study the collective influence of ECM composition and density on the contractile mechanics of human MDA-MB-231 cells making use of the recently established trypsin deadhesion assay. Using collagen and fibronectin-coated surfaces of varying density, we show that cell contractility is tuned in a density-dependent manner, with faster deadhesion on fibronectin-coated surfaces compared to collagen-coated surfaces under identical coating densities. The deadhesion responses are significantly delayed when cells are treated with the myosin...
Methods in Cell Biology, 2007
It is increasingly appreciated that the elasticity of the microenvironment around cells exerts a ... more It is increasingly appreciated that the elasticity of the microenvironment around cells exerts a significant influence on cell behavior, but careful consideration of what is the physiologically relevant elasticity for specific cell types is required to produce meaningful results that fully recapitulate in vivo development. Here we describe methodological details for excising and characterizing the eVective microelasticity of tissues; but first we describe and validate an atomic force microscopy (AFM) method as applied to two comparatively simple hydrogel systems. With
Biophysical Journal, 2010
Glioblastoma Multiforme (GBM) is a malignant astrocytic tumor associated with low survival rates ... more Glioblastoma Multiforme (GBM) is a malignant astrocytic tumor associated with low survival rates because of aggressive infiltration of tumor cells into the brain parenchyma. Expression of the actin binding protein a-actinin has been strongly correlated with the invasive phenotype of GBM in vivo. To probe the cellular basis of this correlation, we have suppressed expression of the nonmuscle isoforms a-actinin-1 and a-actinin-4 and examined the contribution of each isoform to the structure, mechanics, and motility of human glioma tumor cells in culture. While subcellular localization of each isoform is distinct, suppression of either isoform yields a phenotype that includes dramatically reduced motility, compensatory upregulation and redistribution of vinculin, reduced cortical elasticity, and reduced ability to adapt to changes in the elasticity of the extracellular matrix (ECM). Mechanistic studies reveal a relationship between a-actinin and non-muscle myosin II in which depletion of either a-actinin isoform reduces myosin expression and maximal cell-ECM tractional forces. Our results demonstrate that both a-actinin-1 and a-actinin-4 make critical and distinct contributions to cytoskeletal organization, rigidity-sensing, and motility of glioma cells, thereby yielding mechanistic insight into the observed correlation between a-actinin expression and GBM invasiveness in vivo.
International journal of cell biology, 2012
The extracellular matrix (ECM) is known to provide various physicochemical cues in directing cell... more The extracellular matrix (ECM) is known to provide various physicochemical cues in directing cell behavior including composition, topography, and dimensionality. Physical remodeling of the ECM has been documented in a variety of cancers. In breast cancer, the increased deposition of matrix proteins, their crosslinking, and alignment create a stiffer microenvironment that activates cell contractility and promotes cancer invasion. In this paper, we sought to study the collective influence of ECM composition and density on the contractile mechanics of human MDA-MB-231 cells making use of the recently established trypsin deadhesion assay. Using collagen and fibronectin-coated surfaces of varying density, we show that cell contractility is tuned in a density-dependent manner, with faster deadhesion on fibronectin-coated surfaces compared to collagen-coated surfaces under identical coating densities. The deadhesion responses are significantly delayed when cells are treated with the myosin...
Methods in Cell Biology, 2007
It is increasingly appreciated that the elasticity of the microenvironment around cells exerts a ... more It is increasingly appreciated that the elasticity of the microenvironment around cells exerts a significant influence on cell behavior, but careful consideration of what is the physiologically relevant elasticity for specific cell types is required to produce meaningful results that fully recapitulate in vivo development. Here we describe methodological details for excising and characterizing the eVective microelasticity of tissues; but first we describe and validate an atomic force microscopy (AFM) method as applied to two comparatively simple hydrogel systems. With