Wörthmüller, D. | Search bioRxiv

bioRxiv2025

Modelling mechanochemical coupling in optogenetically activated cell layers

In adherent cells, actomyosin contractility is regulated mainly by the RhoA signaling pathway, which can be controlled by optogenetics. To model the mechanochemical coupling in such systems, we introduce a finite element framework based on the discontinuous Galerkin method, which allows us to treat cell doublets, chains of cells and monolayers within the same conceptual framework. While the adherent cell layer is modeled as an actively contracting viscoelastic material on an elastic foundation, different models are considered for the Rho-pathway, starting with a simple linear chain that can be solved analytically and later including direct feedback that can be solved only numerically. Our model predicts signal propagation as a function of coupling strength and viscoelastic time scales and identifies the conditions for optimal cell responses and wave propagation. In general, it provides a systematic understanding of how biochemistry and mechanics simultaneously contribute to the communication of adherent cells.

biophysics↗

bioRxiv2022

Grand canonical Brownian dynamics simulations of adsorption and self-assembly of SAS-6 rings on a surface

The protein SAS-6 forms dimers, which then self-assemble into rings that are critical for the nine-fold symmetry of the centriole organelle. It has recently been shown experimentally that the self-assembly of SAS-6 rings is strongly facilitated on a surface, shifting the reaction equilibrium by four orders of magnitude compared to the bulk. Moreover, a fraction of non-canonical symmetries (i.e., different from nine) was observed. In order to understand which aspects of the system are relevant to ensure efficient self-assembly and selection of the nine-fold symmetry, we have performed Brownian dynamics computer simulation with patchy particles and then compared our results with experimental ones. Adsorption onto the surface was simulated by a Grand Canonical Monte Carlo procedure and Random Sequential Adsorption kinetics. Furthermore, self-assembly was described by Langevin equations with hydrodynamic mobility matrices. We find that as long as the interaction energies are weak, the assembly kinetics can be described well by the coagulation-fragmentation equations in the reaction-limited approximation. By contrast, larger interaction energies lead to kinetic trapping and diffusion-limited assembly. We find that selection of nine-fold symmetry requires a small value for the angular interaction range. These predictions are confirmed by the experimentally observed reaction constant and angle fluctuations. Overall, our simulations suggest that the SAS-6 system works at the crossover between a relatively weak binding energy that avoids kinetic trapping and a small angular range that favors the nine-fold symmetry.

biophysics↗