On the mechanical response of the actomyosin cortex during cell indentations
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ORIGINAL PAPER
On the mechanical response of the actomyosin cortex during cell indentations João P. S. Ferreira1,2,3 · Mei Kuang3 · Marco Marques1,2 · Marco P. L. Parente1 · Margot S. Damaser3,4 · Renato M. Natal Jorge1,2 Received: 9 October 2019 / Accepted: 2 April 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract A mechanical model is presented to analyze the mechanics and dynamics of the cell cortex during indentation. We investigate the impact of active contraction on the cross-linked actin network for different probe sizes and indentation rates. The essential molecular mechanisms of filament stretching, cross-linking and motor activity, are represented by an active and viscous mechanical continuum. The filaments behave as worm-like chains linked either by passive rigid linkers or by myosin motors. In the first example, the effects of probe size and loading rate are evaluated using the model for an idealized rounded cell shape in which properties are based on the results of parallel-plate rheometry available in the literature. Extreme cases of probe size and indentation rate are taken into account. Afterward, AFM experiments were done by engaging smooth muscle cells with both sharp and spherical probes. By inverse analysis with finite element software, our simulations mimicking the experimental conditions show the model is capable of fitting the AFM data. The results provide spatiotemporal dependence on the size and rate of the mechanical stimuli. The model captures the general features of the cell response. It characterizes the actomyosin cortex as an active solid at short timescales and as a fluid at longer timescales by showing (1) higher levels of contraction in the zones of high curvature; (2) larger indentation forces as the probe size increases; and (3) increase in the apparent modulus with the indentation depth but no dependence on the rate of the mechanical stimuli. The methodology presented in this work can be used to address and predict microstructural dependence on the force generation of living cells, which can contribute to understanding the broad spectrum of results in cell experiments. Keywords Continuum mechanics · Full-network model · AFM · Actin · Myosin · Cortex · Smooth muscle cell
1 Introduction Cell mechanics govern essential aspects of cellular and subcellular functions such as cell adhesion, migration and differentiation (Elosegui-Artola et al. 2016; Hui et al. 2014; Swift et al. 2013). The cortex, cytoplasm and nucleus each have uniquely different properties, and dysfunctions of * João P. S. Ferreira [email protected] 1
Mechanical Engineering Department, Faculty of Engineering, Porto, Portugal
2
Institute of Science and Innovation in Mechanical and Industrial Engineering (INEGI), Porto, Portugal
3
Department of Biomedical Engineering, Lerner Research Institute, The Cleveland Clinic, Cleveland, OH, USA
4
Advanced Platform Technology Center, Louis Stokes Cleveland VA Medical Center, Cleveland, OH, USA
these substructures are strongly asso
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