Tensegrity and Motor-Driven Effective Interactions in a Model Cytoskeleton

Actomyosin networks are major structural components of the cell. They provide mechanical integrity and allow dynamic remodeling of eukaryotic cells, self-organizing into the diverse patterns essential for development. We provide a theoretical framework to investigate the intricate interplay between local force generation, network connectivity and collective action of molecular motors. This framework is capable of accommodating both regular and heterogeneous pattern formation, arrested coarsening and macroscopic contraction in a unified manner. We model the actomyosin system as a motorized cat's cradle consisting of a crosslinked network of nonlinear elastic filaments subjected to spatially anti-correlated motor kicks acting on motorized (fibril) crosslinks. The phase diagram suggests there can be arrested phase separation which provides a natural explanation for the aggregation and coalescence of actomyosin condensates. Simulation studies confirm the theoretical picture that a nonequilibrium many-body system driven by correlated motor kicks can behave as if it were at an effective equilibrium, but with modified interactions that account for the correlation of the motor driven motions of the actively bonded nodes. Regular aster patterns are observed both in Brownian dynamics simulations at effective equilibrium and in the complete stochastic simulations. The results show that large-scale contraction requires correlated kicking.Comment: 38 pages, 13 figure

Contact inhibition of locomotion and mechanical cross-talk between cell-cell and cell-substrate adhesion determines the pattern of junctional tension in epithelial cell aggregates

We generated a computational approach to analyze the biomechanics of epithelial cell aggregates, either island or stripes or entire monolayers, that combines both vertex and contact-inhibition-of-locomotion models to include both cell-cell and cell-substrate adhesion. Examination of the distribution of cell protrusions (adhesion to the substrate) in the model predicted high order profiles of cell organization that agree with those previously seen experimentally. Cells acquired an asymmetric distribution of basal protrusions, traction forces and apical aspect ratios that decreased when moving from the edge to the island center. Our in silico analysis also showed that tension on cell-cell junctions and apical stress is not homogeneous across the island. Instead, these parameters are higher at the island center and scales up with island size, which we confirmed experimentally using laser ablation assays and immunofluorescence. Without formally being a 3-dimensional model, our approach has the minimal elements necessary to reproduce the distribution of cellular forces and mechanical crosstalk as well as distribution of principal stress in cells within epithelial cell aggregates. By making experimental testable predictions, our approach would benefit the mechanical analysis of epithelial tissues, especially when local changes in cell-cell and/or cell-substrate adhesion drive collective cell behavior.Comment: 39 pages, 8 Figures. Supplementary Information is include