Switching behaviour in vascular smooth muscle cell–matrix adhesion during oscillatory loading
Irons, Linda; Huang, Huang; Owen, Markus R.; O'Dea, Reuben D; Meininger, Gerald A; Brook, Bindi S.
Professor MARKUS OWEN firstname.lastname@example.org
Professor of Mathematical Biology
REUBEN O'DEA REUBEN.ODEA@NOTTINGHAM.AC.UK
Gerald A Meininger
BINDI BROOK email@example.com
Integrins regulate mechanotransduction between smooth muscle cells (SMCs) and the extracellular matrix (ECM). SMCs resident in the walls of airways or blood vessels are continuously exposed to dynamic mechanical forces due to breathing or pulsatile blood flow. However, the resulting effects of these forces on integrin dynamics and associated cell-matrix adhesion are not well understood. Here we present experimental results from atomic force microscopy (AFM) experiments, designed to study the integrin response to external oscillatory loading of varying amplitudes applied to live aortic SMCs, together with theoretical results from a mathematical model. In the AFM experiments, a fibronectin-coated probe was used cyclically to indent and retract from the surface of the cell. We observed a transition between states of firm adhesion and of complete detachment as the amplitude of oscillatory loading increased, revealed by qualitative changes in the force timecourses. Interestingly, for some of the SMCs in the experiments, switching behaviour between the two adhesion states is observed during single timecourses at intermediate amplitudes. We obtain two qualitatively similar adhesion states in the mathematical model, where we simulate the cell, integrins and ECM as an evolving system of springs, incorporating local integrin binding dynamics. In the mathematical model, we observe a region of bistability where both the firm adhesion and detachment states can occur depending on the initial adhesion state. The differences are seen to be a result of mechanical cooperativity of integrins and cell deformation. Switching behaviour is a phenomenon associated with bistability in a stochastic system, and bistability in our deter-ministic mathematical model provides a potential physical explanation for the experimental results. Physiologically, bistability provides a means for transient mechanical stimuli to induce long-term changes in adhesion dynamics-and thereby the cells' ability to transmit force-and we propose further experiments for testing this hypothesis.
Irons, L., Huang, H., Owen, M. R., O'Dea, R. D., Meininger, G. A., & Brook, B. S. (2020). Switching behaviour in vascular smooth muscle cell–matrix adhesion during oscillatory loading. Journal of Theoretical Biology, 502, https://doi.org/10.1016/j.jtbi.2020.110387
|Journal Article Type||Article|
|Acceptance Date||Jun 17, 2020|
|Online Publication Date||Jun 27, 2020|
|Publication Date||Oct 7, 2020|
|Deposit Date||Jun 24, 2020|
|Publicly Available Date||Jun 28, 2021|
|Journal||Journal of Theoretical Biology|
|Peer Reviewed||Peer Reviewed|
|Keywords||integrins; dynamic loading; mechanotransduction; bistability|
|Additional Information||This article is maintained by: Elsevier; Article Title: Switching behaviour in vascular smooth muscle cell–matrix adhesion during oscillatory loading; Journal Title: Journal of Theoretical Biology; CrossRef DOI link to publisher maintained version: https://doi.org/10.1016/j.jtbi.2020.110387; Content Type: article; Copyright: © 2020 Elsevier Ltd. All rights reserved.|
This file is under embargo until Jun 28, 2021 due to copyright restrictions.
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