Cooperative Coupling of Cell-Matrix and Cell–Cell Adhesions in Cardiac Muscle
Cooperative coupling of cell-matrix and cell–cell adhesions in cardiac muscle Megan L. McCaina, Hyungsuk Leea,1, Yvonne Aratyn-Schausa, André G. Kléberb, and Kevin Kit Parkera,2 aDisease Biophysics Group, Wyss Institute for Biologically Inspired Engineering, School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138; and bDepartment of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215 Edited by Robert Langer, Massachusetts Institute of Technology, Cambridge, MA, and approved May 1, 2012 (received for review February 21, 2012) Adhesion between cardiac myocytes is essential for the heart to serve as cues for remodeling adhesions and assembling tissues. In function as an electromechanical syncytium. Although cell-matrix vitro studies have demonstrated that cytoskeletal tension (27) and and cell–cell adhesions reorganize during development and dis- exogenous cyclic strain (28, 29) promote cell–cell adhesion and ease, the hierarchical cooperation between these subcellular struc- tissue assembly in many cell types. Culturing noncardiac cells tures is poorly understood. We reasoned that, during cardiac on stiff substrates tips the balance of adhesion in favor of focal development, focal adhesions mechanically stabilize cells and tis- adhesions and away from cell–cell adhesions (30–32), suggesting sues during myofibrillogenesis and intercalated disc assembly. As that mechanical forces can modulate the assembly or disassembly the intercalated disc matures, we postulated that focal
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