Self-organization of muscle cell structure and function
| Autor: | William J. Adams, Po-Ling Kuo, Mark-Anthony Bray, Anna Grosberg, Chin-Lin Guo, Kevin Kit Parker, Sean P. Sheehy, Nicholas A. Geisse |
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| Přispěvatelé: | Crampin, Edmund J |
| Rok vydání: | 2011 |
| Předmět: |
02 engineering and technology
Sarcomere Mathematical Sciences Physiology/Muscle and Connective Tissue Extracellular matrix Rats Sprague-Dawley Myofibrils Models Myocyte Myocytes Cardiac Physiology/Morphogenesis and Cell Biology Cytoskeleton lcsh:QH301-705.5 Cells Cultured 0303 health sciences Cultured Ecology Cell Biology/Extra-Cellular Matrix Biological Sciences 021001 nanoscience & nanotechnology Immunohistochemistry Cell biology Computational Theory and Mathematics Modeling and Simulation Physiology/Pattern Formation Biophysics/Experimental Biophysical Methods medicine.symptom 0210 nano-technology Cardiac Muscle contraction Research Article Muscle Contraction Sarcomeres Bioinformatics Cells Biology Models Biological Focal adhesion 03 medical and health sciences Cellular and Molecular Neuroscience Cell Biology/Cytoskeleton Information and Computing Sciences Genetics medicine Animals Biophysics/Cell Signaling and Trafficking Structures Computer Simulation Molecular Biology Ecology Evolution Behavior and Systematics Actin 030304 developmental biology Focal Adhesions Myocytes Physiology/Cardiovascular Physiology and Circulation Biological Actins Rats Cell Biology/Cell Adhesion lcsh:Biology (General) Musculoskeletal Sprague-Dawley Myofibril Mathematics |
| Zdroj: | PLoS computational biology, vol 7, iss 2 PLoS Computational Biology PLoS Computational Biology, Vol 7, Iss 2, p e1001088 (2011) |
| Popis: | 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. Author Summary How muscle is organized impacts its function. However, understanding how muscle organizes is challenging, as the process occurs over several length scales. We approach this multiscale coupling problem by constraining the overall shapes of muscle cells to indirectly control the organization of their intracellular space. We hypothesized the cellular boundary conditions direct the organization of cytoskeletal scaffolds. We developed a model of how the cytoskeleton of cardiomyocytes organizes with respect to boundary cues. Our computational and experimental results to control myocyte shape indicated that distinct muscle architectures arise from two main organizational mechanisms: the interaction between actin fibers, premyofibrils and focal adhesions, as well as cooperative alignment and parallel bundling of more mature myofibrils. We show that a hierarchy of processes regulate the self-organization of cardiomyocytes. Our results suggest that a symmetry break, due to the boundary conditions imposed on the cell, is responsible for polarization of the contractile cytoskeletal organization. |
| Databáze: | OpenAIRE |
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