16 Dec 2011
Sheetz Group, Department of Biological Sciences
Cell sensing of substrate rigidity is a critical function in both unicellular and multicellular organisms, and its breakdown is associated with many diseases. Here, I suggest that two recent discoveries in mammalian fibroblasts: 1) protrusion-retraction cycles of roughly 20s, accompanied by large-scale lateral waves at the leading edge on continuum substrates, and 2) a local contraction unit on micron scale able to generate constant displacements of elastomer pillars independent on the their stiffness, are two aspects of the same mechanism the cell uses during early spreading to sense substrate rigidity. Force map movies on pillars show protrusion-retraction cycles corresponding to organization of local contractions in a characteristic pattern along the cell leading edge. I will describe live images, with seconds and submicron resolution, in which fluorescent myosin, alpha-actinin, and different focal adhesion proteins display spatiotemporal correlations between their concentrations and the forces applied on pillars, suggesting alpha-actinin as a major force bearing protein. Taken all together these results suggest that the full dynamics of a spreading cell is given by the combined effect of local contractions on micron scale along the cell edge, and coupling of focal adhesion complexes with the actin rearward flow, which takes place on a larger space scale.
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