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First published online November 5, 2008

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ECM – at the heart of cell function

The stiffness of the extracellular matrix (ECM) – which varies considerably between tissues – influences cell shape, protein expression and differentiation, and is important for tissue function. In the heart, for instance, the ECM to which cardiomyocytes attach must be sufficiently compliant for the heart to beat in response to actomyosin contraction. Fibrotic scars – which are considerably stiffer than normal myocardium – are present in the heart after myocardial infarction, but how do they affect cardiomyocyte function? On page 3794, Dennis Discher and colleagues address this question by culturing embryonic cardiomyocytes on a series of substrates of differing elasticity. The authors show that the transmission of contractile work (cardiomyocyte beating) to the matrix is optimal on matrices that mimic the elasticity of the developing myocardial microenvironment. By contrast, cells growing on stiffer substrates (which mimic a fibrotic scar) transmit little work to the matrix; moreover, they are deficient in myofibril assembly and their beating frequency slows over time. The authors use an in-situ cysteine-shotgun approach to identify several key differences in protein conformation or assembly between cells grown on myocardium- and fibrosis-like substrates. Their data highlight the likely importance of mechanical microenvironments in pathogenesis.

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Related articles in JCS:

Embryonic cardiomyocytes beat best on a matrix with heart-like elasticity: scar-like rigidity inhibits beating

Adam J. Engler, Christine Carag-Krieger, Colin P. Johnson, Matthew Raab, Hsin-Yao Tang, David W. Speicher, Joseph W. Sanger, Jean M. Sanger, and Dennis E. Discher
JCS 2008 121: 3794-3802. [Abstract] [Full Text]  

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in JCS Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Search for Related Content Social Bookmarking                         What's this?