Understanding cytoskeletal avalanches using mechanical stability analysis

Abstract

Eukaryotic cells are mechanically supported by a polymer network called the cytoskeleton, which consumes chemical energy to dynamically remodel its structure. Recent experiments in vivo have revealed that this remodeling occasionally happens through anomalously large displacements, reminiscent of earthquakes or avalanches. These cytoskeletal avalanches might indicate that the cytoskeleton’s structural response to a changing cellular environment is highly sensitive, and they are therefore of significant biological interest. However, the physics underlying “cytoquakes” is poorly understood. Here, we use agent-based simulations of cytoskeletal self-organization to study fluctuations in the network’s mechanical energy. We robustly observe non-Gaussian statistics and asymmetrically large rates of energy release compared to accumulation in a minimal cytoskeletal model. The large events of energy release are found to correlate with large, collective displacements of the cytoskeletal filaments. We also find that the changes in the localization of tension and the projections of the network motion onto the vibrational normal modes are asymmetrically distributed for energy release and accumulation. These results imply an avalanche-like process of slow energy storage punctuated by fast, large events of energy release involving a collective network rearrangement. We further show that mechanical instability precedes cytoquake occurrence through a machine-learning model that dynamically forecasts cytoquakes using the vibrational spectrum as input. Our results provide a connection between the cytoquake phenomenon and the network’s mechanical energy and can help guide future investigations of the cytoskeleton’s structural susceptibility.

Forecasting Avalanches in Branched Actomyosin Networks with Network Science and Machine Learning

“…It is indicative that the avalanche is a mechanically dominant, common phenomenon in the simulated actomyosin systems. Although this finding is consistent with that of another work about avalanches risen from unbranched actomyosin networks, 53 our independent work embraces the emergence of structural hierarchy in a network from sudden topological changes in the nanoarchitectures of branched actomyosin filaments.…”

On Stretching, Bending, Shearing, and Twisting of Actin Filaments I: Variational Models

“…In MEDYAN, the system’s dynamics are propagated forward via short bursts of stochastic chemical activity over a reaction-diffusion compartment grid followed by periodic relaxation of the system’s mechanical energy; this allows for efficient simulations that include chemical reactions with spatially varying propensities. , We note that this energy-minimization based approach to dynamics neglects the thermal diffusive motion of the filaments. The rationale behind this approach is that the ATP-consuming contributions to the system dynamics, coming from myosin motor steps and actin polymerization, significantly outweighs the contributions coming from diffusive motion of the filaments in these far-from-equilibrium systems. ,, As a result, neglecting thermal motion in MEDYAN simulations is not expected to significantly compromise the realism of the behaviors in which we are interested, and this claim has been corroborated through several validations of MEDYAN predictions against experimental measurements. − Under some external loads, such as cross-linkers bound to the filament, the energy E is variationally minimized for some continuous functions r ★ ( ŝ ) and Q ★ ( ŝ ), where the star denotes the energy-minimized configuration. This infinite-dimensional functional minimization problem is computationally burdensome, necessitating a more efficient scheme for scalable simulations.…”

Optogenetic Miro cleavage reveals direct consequences of real-time loss of function inDrosophila

“…It would be interesting in future investigations to establish whether the phenotype that we observe could be regarded as a 'mitoquake', i.e. rapid mitochondrial network disruption with associated release of mechanical energy, similar to the sudden cytoskeletal rearrangements ('cytoquakes') that were proposed to underpin mechanical adaptivity during cellular dynamic processes (Floyd et al, 2021).…”