Contractile to extensile transitions and mechanical adaptability enabled by activity in cytoskeletal structures

Cytoskeletal network architecture is crucial in determining emergent morphology and dynamics, particularly in processes like stress fiber nucleation, where cells respond to mechanical cues. However, a clear understanding of the connection between architecture, dynamics, and mechanical response remains lacking. In this study, we investigate how self-assembled cytoskeletal structures respond to external mechanical perturbations, focusing on filament and crosslinker mixtures in two dimensions. Using agent-based models complemented by coarse-grained thermodynamic analysis, we reveal how molecular motor activity enables cytoskeletal structures to robustly adapt to changing mechanical conditions. Our simulations demonstrate that under tensile forces, self-assembled active asters transform into bundle-like structures, reminiscent of de novo stress fiber formation in living cells, while pre-existing active bundles elongate further in a reproducible and regulated manner. In contrast, passive assemblies exhibit no such qualitative morphological reorganization, highlighting the critical role of activity in mechanical adaptation. We derive a simple relation approximating active stress as a function of average relative motor alignment, a measure of mesoscopic architecture, which allows us to predict changes in stress characteristics in response to mechanical perturbations with or without morphological reorganization. Our results demonstrate how mesoscopic architecture and motor activity work in tandem to enable robust morphological and mechanical adaptation in cytoskeletal structures, providing insight into cellular mechanosensing and stress fiber formation.

Cytoskeletal networks adapt for optimal functionality in a dynamic intra-cellular environment. However, how adaptability emerges from local network architecture and their activity remains elusive. Here, we use specialized simulations and theory to study the response of cytoskeletal network structures, such as asters and bundles, to mechanical perturbation and show how activity enables robust morphological adaptation. Further, we show how the emergent contractile or extensile nature of these network structures is determined by a mesoscale architectural metric measured as average relative motor alignment. The mechanical adaptation emerges from changes in this architectural metric due to mechanical perturbations.