Physically-Based Structural Modelling of a Typical Regenerative Tissue Analog Elucidates and Bridges the Material Macroscale and the Cellular Microscale

The debates and controversies in mechanobiology are largely attributable to the lack of a sophisticated structural formalism for bridging the macroscale of material mechanical properties and the microscale of cellular perception. This study presents the most comprehensive structural modelling to date on the passive and active processes in a typical tissue model, respectively, by means of a sinusoidal fibrillar network with its geometric entropy for the macroscale characteristics of filamentous materials and a deterministic molecular clutch model for the microscale cell mechanobiological sensing. The elucidation of the macroscale properties, and in particular of the anomalous Poisson effect substantially validate our modelling of the fibrillar configuration and network effects for the analysis of the cell-matrix interaction. The cellular ascending and descending portions over the entire elastic range of the micro-environment are revealed and on top of that the hierarchical features of cellular perception are highlighted. The methodologies provided in this study for modelling the filamentous material and the cell-matrix interaction deliver deep insight into the temporospatial dynamics of 3D cell-matrix interaction, and are able to bridge the cellular microscale and material macroscale in the exploration of related topics in mechanobiology.