Hybrid cellular Potts and bead-spring modeling of cells in fibrous extracellular matrix.

Autor:	Tsingos E; Mathematical Institute, Leiden University, Leiden, the Netherlands. Electronic address: e.tsingos@math.leidenuniv.nl., Bakker BH; Mathematical Institute, Leiden University, Leiden, the Netherlands., Keijzer KAE; Mathematical Institute, Leiden University, Leiden, the Netherlands., Hupkes HJ; Mathematical Institute, Leiden University, Leiden, the Netherlands., Merks RMH; Mathematical Institute, Leiden University, Leiden, the Netherlands; Institute for Biology Leiden, Leiden University, Leiden, the Netherlands. Electronic address: merksrmh@math.leidenuniv.nl.
Jazyk:	angličtina
Zdroj:	Biophysical journal [Biophys J] 2023 Jul 11; Vol. 122 (13), pp. 2609-2622. Date of Electronic Publication: 2023 May 13.
DOI:	10.1016/j.bpj.2023.05.013
Abstrakt:	The mechanical interaction between cells and the extracellular matrix (ECM) is fundamental to coordinate collective cell behavior in tissues. Relating individual cell-level mechanics to tissue-scale collective behavior is a challenge that cell-based models such as the cellular Potts model (CPM) are well-positioned to address. These models generally represent the ECM with mean-field approaches, which assume substrate homogeneity. This assumption breaks down with fibrous ECM, which has nontrivial structure and mechanics. Here, we extend the CPM with a bead-spring model of ECM fiber networks modeled using molecular dynamics. We model a contractile cell pulling with discrete focal adhesion-like sites on the fiber network and demonstrate agreement with experimental spatiotemporal fiber densification and displacement. We show that at high network cross-linking, contractile cell forces propagate over at least eight cell diameters, decaying with distance with power law exponent n= 0.35 - 0.65 typical of viscoelastic ECMs. Further, we use in silico atomic force microscopy to measure local cell-induced network stiffening consistent with experiments. Our model lays the foundation for investigating how local and long-ranged cell-ECM mechanobiology contributes to multicellular morphogenesis. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2023 Biophysical Society. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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