High-resolution micromechanical measurement in real time of forces exerted by living cells

Abstract

The aim of this study was to compare uniaxial traction forces exerted by different cell types using a novel sensor design and to test the dependence of measured forces on cytoskeletal integrity. The sensor design detects forces generated between 2 contact points by cells spanning a gap. The magnitude of these forces varied according to cell type and were dependent on cytoskeletal integrity. The response time for drug-induced cytoskeletal disruption also varied between cell types: dermal fibroblasts exerted the greatest forces and had the slowest drug response times; EBV-transformed epithelial cells also had slow cytoskeletal depolymerisation times but exerted the lowest forces overall. Conversely, lung epithelial tumor cells exerted low forces but had the fastest depolymerisation drug response. These results provide proof of principle for a new design of force-measurement sensor based on optical interferometry, an approach that can be used to study cytoskeletal dynamics in real time.

The Role of Cell Adhesion and Cytoskeleton Dynamics in the Pathogenesis of the Ehlers-Danlos Syndromes and Hypermobility Spectrum Disorders

“…One is cell adhesion to collagen via integrins, as blocking integrin-mediated adhesion with antibodies prevented gel contraction ( Klein et al, 1991 ; Schiro et al, 1991 ; Kelynack et al, 2000 ). Equally important is an active cytoskeleton, as using molecular inhibitors that interfere with actin filament and microtubule polymerization abrogates tractional force generation and reduces tension within the gel ( Kolodney and Wysolmerski, 1992 ; Swierczewski et al, 2016 ; Giannopoulos et al, 2018 ). The involvement of intermediate filaments has also been indicated in this process, as vimentin-null fibroblasts show a reduced ability to contract the gel ( Ridge et al, 2016 ).…”