Self-organization of muscle cell structure and function

• Published in: PLoS computational biology Vol. 7; no. 2; p. e1001088
• Main Authors: Grosberg, Anna, Kuo, Po-Ling, Guo, Chin-Lin, Geisse, Nicholas A, Bray, Mark-Anthony, Adams, William J, Sheehy, Sean P, Parker, Kevin Kit
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.02.2011; Public Library of Science (PLoS)
• Subjects: Actins - metabolism; Animals; Architectural engineering; Biophysics/Cell Signaling and Trafficking Structures; Biophysics/Experimental Biophysical Methods; Boundary conditions; Cardiomyocytes; Cell Biology/Cell Adhesion; Cell Biology/Cytoskeleton; Cell Biology/Extra-Cellular Matrix; Cell culture; Cells, Cultured; Computer Simulation; Cytoskeleton; Cytoskeleton - metabolism; Cytoskeleton - physiology; Experiments; Focal Adhesions - chemistry; Focal Adhesions - physiology; Immunohistochemistry; Mathematics; Models, Biological; Muscle cells; Muscle Contraction - physiology; Muscular system; Myocytes, Cardiac - cytology; Myocytes, Cardiac - metabolism; Myocytes, Cardiac - physiology; Myofibrils - chemistry; Myofibrils - metabolism; Myofibrils - physiology; Physiology/Cardiovascular Physiology and Circulation; Physiology/Morphogenesis and Cell Biology; Physiology/Muscle and Connective Tissue; Physiology/Pattern Formation; Proteins; Rats; Rats, Sprague-Dawley; Sarcomeres - metabolism; Sarcomeres - physiology; Structure; Studies; Symmetry; United States; Immunohistochemistry; Myocytes, Cardiac; Cells, Cultured; Actins; Focal Adhesions; Rats; Rats, Sprague-Dawley; Myofibrils; Animals; Muscle Contraction; Models, Biological; Computer Simulation; Cytoskeleton; Sarcomeres
• ISSN: 1553-7358; 1553-734X; 1553-7358
• DOI: 10.1371/journal.pcbi.1001088

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.