"Building Contractile Machines in the Cytoskeleton"

The ability to spatially and temporally regulate forces drives a diverse array of biological process, including cell division, migration and morphogenesis. These processes span the subcellular to tissue length scales, and yet are driven by the same basic set of molecular components. While significant progress has been made in understanding the mechanochemistry of single proteins, we lack an understanding of how larger length scale behaviors emerge from the coordinated activity of thousands of simultaneous molecular interactions. In this talk, I will examine this issue within the context of how cells regulate the distribution of traction stresses in adherent cells. First, using a combination of micropatterning to control cell shape, and traction force microscopy to measure stresses generated by cells, I will show that cell area is the dominant regulator of contractile work in adherent cells. Changes in cell shape determine the distribution of contractile work done against the substrate, but do not affect the total work performed by the cell. Second, I will show that these findings can be robustly captured by a model of the cell as a uniformly contracting gel with a line tension. Finally, I will explore the molecular mechanisms underlying our physical model and our ability to modulate the contractile behavior of cells through physical, biochemical and optogenetic approaches.

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