Dataset Information

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

ABSTRACT: 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.

SUBMITTER: Tsingos E

PROVIDER: S-EPMC10397577 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Tsingos Erika E Bakker Bente Hilde BH Keijzer Koen A E KAE Hupkes Hermen Jan HJ Merks Roeland M H RMH

Biophysical journal 20230513 13

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 ...[more]

PMID: 37183398

Similar Datasets

Project description:Gap closure is a dynamic process in wound healing, in which a wound contracts and a provisional matrix is laid down, to restore structural integrity to injured tissues. The efficiency of wound closure has been found to depend on the shape of a wound, and this shape dependence has been echoed in various in vitro studies. While wound shape itself appears to contribute to this effect, it remains unclear whether the alignment of the surrounding extracellular matrix (ECM) may also contribute. In this study, we investigate the role both wound curvature and ECM alignment have on gap closure in a 3D culture model of fibrous tissue. Using microfabricated flexible micropillars positioned in rectangular and octagonal arrangements, seeded 3T3 fibroblasts embedded in a collagen matrix formed microtissues with different ECM alignments. Wounding these microtissues with a microsurgical knife resulted in wounds with different shapes and curvatures that closed at different rates. Observing different regions around the wounds, we noted local wound curvature did not impact the rate of production of provisional fibronectin matrix assembled by the fibroblasts. Instead, the rate of provisional matrix assembly was lowest emerging from regions of high fibronectin alignment and highest in the areas of low matrix alignment. Our data suggest that the underlying ECM structure affects the shape of the wound as well as the ability of fibroblasts to build provisional matrix, an important step in the process of tissue closure and restoration of tissue architecture. The study highlights an important interplay between ECM alignment, wound shape, and tissue healing that has not been previously recognized and may inform approaches to engineer tissues. Impact statement Current models of tissue growth have identified a role for curvature in driving provisional matrix assembly. However, most tissue repair occurs in fibrous tissues with different levels of extracellular matrix (ECM) alignment. Here, we show how this underlying ECM alignment may affect the ability of fibroblasts to build new provisional matrix, with implications for in vivo wound healing and providing insight for engineering of new tissues.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets