Authors: J Yasha Kresh Anant Chopra
Publish Date: 2011/03/25
Volume: 462, Issue: 1, Pages: 75-87
Abstract
Adult cardiomyocytes are terminally differentiated with minimal replicative capacity Therefore longterm preservation or enhancement of cardiac function depends on structural adaptation Myocytes interact with the extracellular matrix fibroblasts and vascular cells and with each other end to end side to side We review the current understanding of the mechanical determinants and environmental sensing systems that modulate and regulate myocyte molecular machinery and its structural organization We feature the design and application of engineered cellular microenvironments to demonstrate the ability of cardiac cells to remodel their cytoskeletal organization and shape including sarcomere/myofibrillar architectural topography Cell shapedependent functions result from complex mechanical interactions between the cytoskeleton architecture and external conditions be they cell–cell or cell–extracellular matrix ECM adhesion contactmediated This mechanobiological perspective forms the basis for viewing the cardiomyocyte as a mechanostructural anisotropic continuum exhibiting constant mechanosensorydriven selfregulated adjustment of the cytoskeleton through tight interplay between its force generation activity and concurrent cytoarchitectural remodeling The unifying framework guiding this perspective is the observation that these emerging events and properties are initiated by and respond to cytoskeletal reorganization regulated by cell–cell and cell–ECM adhesion and its corresponding mutually interactive signaling machinery It is important for future studies to elucidate how cross talk between these mechanical signals is coordinated to control myocyte structure and function Ultimately understanding how the highly interactive mechanical signaling can give rise to phenotypic changes is critical for targeting the underlying pathways that contribute to cardiac remodeling associated with various forms of dilated and hypertrophic myopathies myocardial infarction heart failure and reverse remodelingThis work was supported in part by the National Institutes of Health and the Pennsylvania Department of Health We are especially grateful to Pamela Fried Drexel University College of Medicine Academic Publishing Services for editorial assistance and to Victor Lin for helping with the image processing
Keywords: