Biophysics of cellular force-sensing and transduction

In the last decade it has become generally acknowledged that the elasticity of the underlying substrates plays an important role for cell culture [1]. Numerous publications describe the impact of the matrix elasticity on cell adhesion, morphology, and motility. As very recently reported by Engler et al. in Cell [2], matrix elasticity can even guide differentiation of adult human stem cells.

Although many issues of cellular force-sensing and transduction have already been elucidated the understanding of the complex interplay of chemo-mechanical and biochemical processes on the molecular level is in its very beginning. Using physically well-defined microenvironments this project aims to a biophysical description of the cell-matrix interactions. The three non-muscle myosin II isoforms (a,b, and c) are essential for the contractility of the actin cytoskeleton and therefore force-sensing. Using inhibitors, it was shown that sensing the matrix stiffness is disabled and further on the cell differentiation process is shut down.

Figure 1: MSC on glass without (A) and with collagen coating (B) as ligand for integrin binding. Well organized stress fibers of actin (stained red) only occur on the collagen coated surface (B). Scalebar represents 20 µm.

Besides the elasticity of the surface other parameters play important roles as well. Figure 1 shows a mesenchymal stem cell MSC on glass (A) and with additional collagen coating (B) as ligand for integrin binding. It is obvious that well organized stress fibers of actin (stained red) only occur on the collagen coated surface (B).

Employing biophysical tools such as atomic force microscope (AFM) and micropipette aspiration combined with fluorescence microscopy we are investigating the molecular aspects of mechano-sensing and –transduction in cells. Special attention is given to the actin cytoskeleton with its non-muscle myosin II and transmembrane proteins that govern the cell-matrix contacts.

References:

[1] Discher, D.E at al., Science, 2005. 310(5751): p. 1139-1143
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[2] Engler, A.J. et al., Cell, 2006. 126: p. 677-689.
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