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

By A. Engler, C. Carag-Krieger, Colin P. Johnson, M. Raab, Hsin-Yao Tang, D. Speicher, Joseph W. Sanger, J. Sanger, Dennis E. Discher. Journal of Cell Science, 2008

890 citations recorded by the source corpus.

Fibrotic rigidification following a myocardial infarct is known to impair cardiac output, and it is also known that cardiomyocytes on rigid culture substrates show a progressive loss of rhythmic beating. Here, isolated embryonic cardiomyocytes cultured on a series of flexible substrates show that matrices that mimic the elasticity of the developing myocardial microenvironment are optimal for transmitting contractile work to the matrix and for promoting actomyosin striation and 1-Hz beating. On hard matrices that mechanically mimic a post-infarct fibrotic scar, cells overstrain themselves, lack striated myofibrils and stop beating; on very soft matrices, cells preserve contractile beating for days in culture but do very little work. Optimal matrix leads to a strain match between cell and matrix, and suggests dynamic differences in intracellular protein structures. A `cysteine shotgun' method of labeling the in situ proteome reveals differences in assembly or conformation of several abundant cytoskeletal proteins, including vimentin, filamin and myosin. Combined with recent results, which show that stem cell differentiation is also highly sensitive to matrix elasticity, the methods and analyses might be useful in the culture and assessment of cardiogenesis of both embryonic stem cells and induced pluripotent stem cells. The results described here also highlight the need for greater attention to fibrosis and mechanical microenvironments in cell therapy and development.

Subfields: Cell Biology, Molecular Biology, Surgery

View Paper: https://www.semanticscholar.org/paper/3165680c91bb8b8dfbfa90b47f6779731c36fda6

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cell Biology

1. Ulrich S. Schwarz
2. Shmuel Safran
3. B. Hinz
4. G. Reilly
5. A. Engler
6. Nikolaos G. Frangogiannis
7. M. Oyen

In Molecular Biology

1. B. Hinz
2. Ulrich S. Schwarz
3. Shmuel Safran
4. A. Engler

In Surgery

1. B. Hinz
2. Nikolaos G. Frangogiannis

Citations in the corpus

• Physics of adherent cells (2013, background): “Experiments on cultured cells plated on flexible substrates have shown that substrate stiffness is one factor that can regulate cytoskeletal order in general, and myofibril assembly in particular (Engler et al., 2004b, 2008; Jacot et al., 2008; Majkut and Discher, 2012; Serena et al., 2010).”
• Intrinsic extracellular matrix properties regulate stem cell differentiation. (2010, background): “However, such thin coatings do not recapitulate the normal mechanical environment of most cell types (Engler et al., 2004c) and can lead to de-differentiation or loss of function in cells (Engler et al., 2008).”
• Extracellular matrix: A dynamic microenvironment for stem cell niche (2014, neutral): “property of a fibrotic scar [84].”
• The myofibroblast: paradigm for a mechanically active cell. (2010, background): “…of cancer cells (Paszek et al., 2005), mesenchymal stem cells (Engler et al., 2006), neurons (Georges et al., 2006), myotubes (Engler et al., 2004), cardiomyocytes (Engler et al., 2008) and fibroblasts (Goffin et al., 2006), with the list of substrate-responsive cell types continuously growing.”