A multiscale approach to modeling the passive mechanical contribution of cells in tissues.

In addition to their obvious biological roles in tissue function, cells often play a significant mechanical role through a combination of passive and active behaviors. This study focused on the passive mechanical contribution of cells in tissues by improving our multiscale model via the addition of cells, which were treated as dilute spherical inclusions. The first set of simulations considered a rigid cell, with the surrounding ECM modeled as (1) linear elastic, (2) Neo-Hookean, and (3) a fiber network. Comparison with the classical composite theory for rigid inclusions showed close agreement at low cell volume fraction. The fiber network case exhibited nonlinear stress-strain behavior and Poisson's ratios larger than the elastic limit of 0.5, characteristics similar to those of biological tissues. The second set of simulations used a fiber network for both the cell (simulating cytoskeletal filaments) and matrix, and investigated the effect of varying relative stiffness between the cell and matrix, as well as the effect of a cytoplasmic pressure to enforce incompressibility of the cell. Results showed that the ECM network exerted negligible compression on the cell, even when the stiffness of fibers in the network was increased relative to the cell. Introduction of a cytoplasmic pressure significantly increased the stresses in the cell filament network, and altered how the cell changed its shape under tension. Findings from this study have implications on understanding how cells interact with their surrounding ECM, as well as in the context of mechanosensation.