Mechanosensitivity of Formin-Actin Interactions

Abstract

Cells are able to sense and adapt to their physical environment, translating mechanical inputs into chemical outcomes. The molecular basis for this fascinating property, referred to as “mechanotransduction”, remains largely unexplored. The actin cytoskeleton, which generates and transmits forces throughout the cell, is certainly a key player in this process. Here, I will focus on the situation where tension is applied to actin filaments that are interacting with formins at their barbed ends. In cells, formins are typically anchored to a substrate and thus undergo a mechanical force as the filament is put under tension. We have studied this situation in vitro, by manipulating individual filaments with a microfluidic flow, as they are nucleated and elongated by formin mDia1 anchored to the bottom of the microchamber. I will show how filament tension in the picoNewton range modulates the elongation rate of the actin filament, the processivity of the formin and its competition with other end-binding proteins. Quantitatively probing these mechanical properties also provides an interesting angle to test molecular models of formin-assisted filament elongation.