Modeling the distinct dynamics and motion of cells residing on the surface and inside morphing soft tissues

Cellular contractility, migration, and extracellular matrix (ECM) mechanics are critical for a wide range of biological processes including embryonic development, wound healing, tissue morphogenesis, and regeneration. Even though the distinct response of cells near the tissue periphery has been previously observed in cell-laden microtissues, including faster kinetics and more prominent cell-ECM interactions, there are currently no models that can fully combine coupled surface and bulk mechanics and kinetics to recapitulate the morphogenic response of these constructs. This paper presents a novel continuum mechanics framework in a total Lagrangian setting and corresponding finite element implementation for understanding the interplay between cellular contractility, migration, and ECM mechanics in dynamically morphing soft tissues accounting for distinct cellular responses in the bulk and the surface of tissues. The major novelty of this approach is that it enables modeling the distinct migratory and mechanical response of cells residing on the tissue surface and the bulk, where concurrently the morphing soft tissues undergoes large deformations. Additionally, the proposed model is validated through simulation results that capture changes in shape and cell concentration for wounded and intact microtissues, enabling the interpretation of experimental data. The numerical procedure, that accounts for mechanosensitive stress generation, large deformations, diffusive migration in the bulk and a distinct mechanism for diffusive migration on deforming surfaces is inspired from recent work on bulk and surface poroelasticity of hydrogels, but in this work a two-field weak form is proposed and is able to alleviate numerical instabilities that were observed in the original method that utilized a three-field formulation.