# Stochastic Ratcheting on a Funneled Energy Landscape is Necessary for Highly Efficient Contractility of Actomyosin Force Dipoles

## TL;DR

This study reveals that passive cross-linkers and active myosin motors synergize through a ratcheting mechanism on a funneled energy landscape, enabling highly efficient contractility in disordered actomyosin networks.

## Contribution

It demonstrates the necessity of stochastic ratcheting on a funneled energy landscape for efficient actomyosin contractility, combining simulations and mean-field theory.

## Key findings

- Passive cross-linkers generate contractile forces in filament pairs.
- Increasing cross-linker binding energy causes kinetic arrest, reducing contractility.
- Passive cross-linkers amplify forces during motor dissociation periods.

## Abstract

Current understanding of how contractility emerges in disordered actomyosin networks of non-muscle cells is still largely based on the intuition derived from earlier works on muscle contractility. This view, however, largely overlooks the free energy gain following passive cross-linker binding, which, even in the absence of active fluctuations, provides a thermodynamic drive towards highly overlapping filamentous states. In this work, we shed light on this phenomenon, showing that passive cross-linkers, when considered in the context of two anti-parallel filaments, generate noticeable contractile forces. However, as binding free energy of cross-linkers is increased, a sharp onset of kinetic arrest follows, greatly diminishing effectiveness of this contractility mechanism, allowing the network to contract only with weakly resisting tensions at its boundary. We have carried out stochastic simulations elucidating this mechanism, followed by a mean-field treatment that predicts how contractile forces asymptotically scale at small and large binding energies, respectively. Furthermore, when considering an active contractile filament pair, based on non-muscle myosin II, we found that the non-processive nature of these motors leads to highly inefficient force generation, due to recoil slippage of the overlap during periods when the motor is dissociated. However, we discovered that passive cross-linkers can serve as a structural ratchet during these unbound motor time spans, resulting in vast force amplification. Our results shed light on the non-equilibrium effects of transiently binding proteins in biological active matter, as observed in the non-muscle actin cytoskeleton, showing that highly efficient contractile force dipoles result from synergy of passive cross-linker and active motor dynamics, via a ratcheting mechanism on a funneled energy landscape.