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

Publisher: Springer Country of Publication: Germany NLM ID: 101135325 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1617-7940 (Electronic) Linking ISSN: 16177940 NLM ISO Abbreviation: Biomech Model Mechanobiol Subsets: MEDLINE

Original Publication: Berlin ; New York : Springer, c2002-

Cell Movement* ; Models, Biological* ; Extracellular Matrix*/metabolism ; Mechanotransduction, Cellular*/physiology; Morphogenesis ; Surface Properties ; Biomechanical Phenomena ; Stress, Mechanical ; Humans ; Computer Simulation ; Finite Element Analysis ; Animals

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 et al. (Biophys J 117(5):975-986, 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 far, 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 undergo large deformations driven by cell contractility. Additionally, the simulation results capture the 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 involving elastocapillary effects, 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 mixed finite element formulation.
Competing Interests: Declarations Conflict of interest The authors declare no Conflict of interest.
(© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

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Keywords: Cell migration; Contractility; Mechanotransduction; Microtissue; Morphogenesis; Wound healing

Date Created: 20240707 Date Completed: 20241112 Latest Revision: 20241112

20241114

10.1007/s10237-024-01870-2

38972940