Matsumoto, E. | bioRxiv Science

bioRxiv2026

Mechanical stretch disrupts intracellular structures under impaired actin integrity in vascular smooth muscle cells

Actin-bundle organization is essential for vascular smooth muscle cell mechanics and is implicated in actin-related diseases. However, it remains unclear how cell stretching affects intracellular actin bundles when actin polymerization is impaired. Here, we performed live imaging of Latrunculin A-treated A7r5 vascular smooth muscle cells in a stretch chamber. GFP--actinin imaging showed that Latrunculin A reduced actin-bundle coverage while periodicity was maintained. Subsequent mechanical stretch disrupted both actin-bundle coverage and periodicity. We constructed a stochastic filament bundle model in which actin filament length, actin crosslinking protein dynamics, external stretch, and myosin-driven contractile shortening determine bundle connectivity. The model generated non-spanning, collapse, and persistent states based on spanning connectivity before and after stretch, shaped by filament length and applied strain. A reduced model further showed that these states are governed by a balance between connectivity formation and stretch-induced loss. Together, our results suggest that reduced actin polymerization destabilizes intracellular actin-bundle organization under mechanical stretch, providing a mechanism linking actin polymerization defects to mechanical fragility in vascular smooth muscle cells.

biophysics↗

bioRxiv2026

A closed-loop mathematical structure of mechanics-turnover coupling for mechanical adaptation in living systems

Mechanical adaptation underlies mechanical homeostasis by allowing living systems to restore characteristic mechanical variables under sustained perturbations. Across biological scales, turnover-mediated remodeling enables mechanical adaptation by continuously renewing internal structures under load. Despite extensive progress in this field, it remains to be established what closed-loop mathematical structure of mechanics-turnover coupling is sufficient to guarantee homeostasis and how the characteristic adaptation timescale emerges from this coupling. Here, we identify the minimal mathematical structure of closed-loop mechanics-turnover coupling, providing a unifying description of mechanically adaptive remodeling across scales. We derive an analytical expression for the adaptation timescale as a function of the coupling between internal mechanical parameters and turnover kinetics, enabling direct cross-system comparison. To isolate this structure, we formulate a dynamical model linking mechanics and turnover, and establish conditions under which the closed-loop dynamics exhibit integral action. Specifically, our model describes how deviations in the mechanical state modulate the turnover of an internal structural state, and the renewed structure feeds back onto mechanics in a negative-feedback direction, driving recovery toward a reference state. We define systems satisfying this structure as Feedback Adaptive Turnover-mediated Environment-Dependent (FATED) systems. As an experimental example, we formulate mechanical adaptation in terms of mechanically regulated actin turnover. With the generalization of this architecture, we evaluate cross-system consistency by comparing reported adaptation and turnover timescales across representative remodeling systems.

biophysics↗