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Self-Organization of Muscle Cell Structure and Function



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Self Organization of Muscle Cell Structure and Function Anna Grosberg Po Ling Kuo Chin Lin Guo Nicholas A Geisse Mark Anthony Bray William J Adams Sean P Sheehy Kevin Kit Parker Disease Biophysics Group Wyss Institute for Biologically Inspired Engineering School of Engineering and Applied Sciences Harvard University Cambridge Massachusetts United States of America Abstract The organization of muscle is the product of functional adaptation over several length scales spanning from the sarcomere to the muscle bundle One possible strategy for solving this multiscale coupling problem is to physically constrain the muscle cells in microenvironments that potentiate the organization of their intracellular space We hypothesized that boundary conditions in the extracellular space potentiate the organization of cytoskeletal scaffolds for directed sarcomeregenesis We developed a quantitative model of how the cytoskeleton of neonatal rat ventricular myocytes organizes with respect to geometric cues in the extracellular matrix Numerical results and in vitro assays to control myocyte shape indicated that distinct cytoskeletal architectures arise from two temporally ordered organizational processes the interaction between actin fibers premyofibrils and focal adhesions as well as cooperative alignment and parallel bundling of nascent myofibrils Our results suggest that a hierarchy of mechanisms regulate the self organization of the contractile cytoskeleton and that a positive feedback loop is responsible for initiating the break in symmetry potentiated by extracellular boundary conditions is required to polarize the contractile cytoskeleton Citation Grosberg A Kuo P L Guo C L Geisse NA Bray M A et al 2011 Self Organization of Muscle Cell Structure and Function PLoS Comput Biol 7 2 e1001088 doi 10 1371 journal pcbi 1001088 Editor Edmund J Crampin University of Auckland New Zealand Received November 24 2009 Accepted January 19 2011 Published February 24 2011 Copyright 2011 Grosberg et



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