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      Phospholipid polymer hydrogel microsphere modulates the cell cycle profile of encapsulated cells

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      Soft Matter

      Royal Society of Chemistry (RSC)

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          Most cited references 30

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          Mechanisms of mechanotransduction.

          Essentially all organisms from bacteria to humans are mechanosensitive. Physical forces regulate a large array of physiological processes, and dysregulation of mechanical responses contributes to major human diseases. A survey of both specialized and widely expressed mechanosensitive systems suggests that physical forces provide a general means of altering protein conformation to generate signals. Specialized systems differ mainly in having acquired efficient mechanisms for transferring forces to the mechanotransducers.
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            Cell-cycle control by physiological matrix elasticity and in vivo tissue stiffening.

            A number of adhesion-mediated signaling pathways and cell-cycle events have been identified that regulate cell proliferation, yet studies to date have been unable to determine which of these pathways control mitogenesis in response to physiologically relevant changes in tissue elasticity. In this report, we use hydrogel-based substrata matched to biological tissue stiffness to investigate the effects of matrix elasticity on the cell cycle. We find that physiological tissue stiffness acts as a cell-cycle inhibitor in mammary epithelial cells and vascular smooth muscle cells; subcellular analysis in these cells, mouse embryonic fibroblasts, and osteoblasts shows that cell-cycle control by matrix stiffness is widely conserved. Remarkably, most mitogenic events previously documented as extracellular matrix (ECM)/integrin-dependent proceed normally when matrix stiffness is altered in the range that controls mitogenesis. These include ERK activity, immediate-early gene expression, and cdk inhibitor expression. In contrast, FAK-dependent Rac activation, Rac-dependent cyclin D1 gene induction, and cyclin D1-dependent Rb phosphorylation are strongly inhibited at physiological tissue stiffness and rescued when the matrix is stiffened in vitro. Importantly, the combined use of atomic force microscopy and fluorescence imaging in mice shows that comparable increases in tissue stiffness occur at sites of cell proliferation in vivo. Matrix remodeling associated with pathogenesis is in itself a positive regulator of the cell cycle through a highly selective effect on integrin-dependent signaling to FAK, Rac, and cyclin D1.
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              Preparation of Phospholipid Polylners and Their Properties as Polymer Hydrogel Membranes

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                Author and article information

                Journal
                SMOABF
                Soft Matter
                Soft Matter
                Royal Society of Chemistry (RSC)
                1744-683X
                1744-6848
                2013
                2013
                : 9
                : 18
                : 4628
                Article
                10.1039/c3sm50394a
                © 2013
                Product
                Self URI (article page): http://xlink.rsc.org/?DOI=c3sm50394a

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