Modeling the mechanosensitive collective migration of cells on the surface and the interior of morphing soft tissues

TL;DR

This paper introduces a novel modeling framework that captures the complex interplay of cellular contractility, migration, and ECM mechanics in morphing soft tissues, accounting for distinct surface and bulk cellular responses during large deformations.

Contribution

The model uniquely combines surface and bulk mechanics with active elastocapillarity to simulate cell migration and tissue morphogenesis in deforming tissues, a capability not previously achieved.

Findings

Model accurately predicts shape changes in microtissues.

Simulations match experimental cell distribution patterns.

Framework enables interpretation of morphogenic responses.

Abstract

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. Mailand \textit{et al.} (2019) had shown the importance of active elastocapillarity in cell-laden microtissues, but modeling the distinct mechanosensitive migration of cells on the periphery and the interior of highly deforming tissues has not been possible thus fur, especially in the presence of active elastocapillary effects. This paper presents a framework 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 contractile response of cells residing on the tissue surface and the bulk, where concurrently the morphing soft tissues undergoes large deformations driven by cell contractility. Additionally, the proposed model is validated through simulation results that capture the changes in shape and cell concentration for wounded and intact microtissues, enabling the interpretation of experimental data.