Entropic, active, and frictional forces in cytoskeletal crosslinking

Abstract

The forces that mixtures of motorized and passive crosslinking proteins collectively generate between cytoskeletal filaments within our cells are the key drivers of active cellular mechanics. Despite their importance, a unified theory connecting measurable crosslinker properties to force generation between filament pairs has so far been missing. In this paper, we derive a theory that predicts the forces generated collectively by crosslinking proteins linking two biopolymer filaments from experimentally accessible filament and crosslinker properties, using out-of-equilibrium thermodynamics. Our framework allows us to decompose the forces generated by crosslinkers into three separate components: entropic, active, and frictional. In doing so, it offers a clear physical interpretation of the fundamental mechanisms by which crosslinking proteins self-organize and collectively generate forces. We demonstrate the robustness and utility of this framework by applying it to four different experiments that probe the combined roles of passive and motorized crosslinkers. For each experiment, our theoretical approach allows us to disentangle the relative contributions of entropic, active, and frictional forces, clarifying how different physical processes underpin collective force production. In turn, this makes it possible to quantitatively compare and predict how various crosslinker combinations influence force generation between filaments, pattern formation along filaments, and the dynamics of filament pairs.