Cell Remote Mechanics Regulates Large-spatial Isotropic Matrix Modeling with Dynamic Simulations

Tissues are often isotropic and heterogeneous organizations, which developmental processes are coordinated by cells and extracellular matrix modeling. Cells have the capability of modeling matrix in distance, however, the biophysical mechanism is largely unknown. We investigated underlying mechanism of large collagen I (COL) fibrillary modeling by cell mechanics with designed arrays of cell clusters. By incorporating dynamic contractions, Molecular Dynamics simulations yielded highly matching isotropic outcomes without spatial limitation to observed COL clustering in experiments from variable geometrical arrays. Further designed single polygons from triangles to hexagons resulted in predicted structural assembly. Cell cytoskeletal integrity (actin filaments, microtubules), actomyosin contractions, and endoplasmic reticulum calcium channels were essential for remote fiber inductions, while membrane mechanosensitive integrin and Piezo showed coordinative role in regulating the fiber assembly. The study provides new insights on cell mechanics-induced isotropic matrix modeling with dynamic large-spatial factors and the associated cellular mechanism, and the assembled biomechanical scaffolds with pre-designs may lead to applications in micro-tissue engineering. This work implicates heterogeneous tissue structures maybe partially derived from isotropic cell mechanics.