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Microscopic biophysical model of self-organization in tissue due to feedback between cell- and macroscopic-scale forces

Hague, JP; Mieczkowski, PW; O'Rourke, C; Loughlin, AJ; Phillips, JB; (2020) Microscopic biophysical model of self-organization in tissue due to feedback between cell- and macroscopic-scale forces. Physical Review Research , 2 (4) , Article 043217. 10.1103/physrevresearch.2.043217. Green open access

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Abstract

We develop a microscopic biophysical model for self-organization and reshaping of artificial tissue, that is codriven by microscopic active forces between cells and an extracellular matrix (ECM), and macroscopic forces that develop within the tissue, finding close agreement with experiment. Microscopic active forces are stimulated by μ m -scale interactions between cells and the ECM within which they exist, and when large numbers of cells act together these forces drive, and are affected by, macroscopic-scale self-organization and reshaping of tissues in a feedback loop. To understand this loop, there is a need to (1) construct microscopic biophysical models that can simulate these processes for the very large number of cells found in tissues, (2) validate and calibrate those models against experimental data, and (3) understand the active feedback between cells and the extracellular matrix, and its relationship to macroscopic self-organization and reshaping of tissue. Our microscopic biophysical model consists of a contractile network representing the ECM, that interacts with a large number of cells via dipole forces, to describe macroscopic self-organization and reshaping of tissue. We solve the model using simulated annealing, finding close agreement with experiments on artificial neural tissue. We discuss the calibration of model parameters. We conclude that feedback between microscopic cell-ECM dipole interactions and tissue-scale forces is a key factor in driving macroscopic self-organization and reshaping of tissue. We discuss the application of the biophysical model to the simulation and rational design of artificial tissues.

Type: Article
Title: Microscopic biophysical model of self-organization in tissue due to feedback between cell- and macroscopic-scale forces
Open access status: An open access version is available from UCL Discovery
DOI: 10.1103/physrevresearch.2.043217
Publisher version: https://doi.org/10.1103/physrevresearch.2.043217
Language: English
Additional information: Published by the American Physical Society under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/). Further distribution of this work must maintain attribution to the author(s) and the published article's title, journal citation, and DOI.
Keywords: Biomechanics, Force sensing, Patterns in complex systems, Self-organization, Self-organized systems
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmacology
URI: https://discovery.ucl.ac.uk/id/eprint/10115747
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