Collective Cell Behavior in Mechanosensing of Substrate Thickness.
Details
Serval ID
serval:BIB_CDD8F75F8608
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Collective Cell Behavior in Mechanosensing of Substrate Thickness.
Journal
Biophysical journal
ISSN
1542-0086 (Electronic)
ISSN-L
0006-3495
Publication state
Published
Issued date
05/06/2018
Peer-reviewed
Oui
Volume
114
Number
11
Pages
2743-2755
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
Publication Status: ppublish
Publication Status: ppublish
Abstract
Extracellular matrix stiffness has a profound effect on the behavior of many cell types. Adherent cells apply contractile forces to the material on which they adhere and sense the resistance of the material to deformation-its stiffness. This is dependent on both the elastic modulus and the thickness of the material, with the corollary that single cells are able to sense underlying stiff materials through soft hydrogel materials at low (<10 μm) thicknesses. Here, we hypothesized that cohesive colonies of cells exert more force and create more hydrogel deformation than single cells, therefore enabling them to mechanosense more deeply into underlying materials than single cells. To test this, we modulated the thickness of soft (1 kPa) elastic extracellular-matrix-functionalized polyacrylamide hydrogels adhered to glass substrates and allowed colonies of MG63 cells to form on their surfaces. Cell morphology and deformations of fluorescent fiducial-marker-labeled hydrogels were quantified by time-lapse fluorescence microscopy imaging. Single-cell spreading increased with respect to decreasing hydrogel thickness, with data fitting to an exponential model with half-maximal response at a thickness of 3.2 μm. By quantifying cell area within colonies of defined area, we similarly found that colony-cell spreading increased with decreasing hydrogel thickness but with a greater half-maximal response at 54 μm. Depth-sensing was dependent on Rho-associated protein kinase-mediated cellular contractility. Surface hydrogel deformations were significantly greater on thick hydrogels compared to thin hydrogels. In addition, deformations extended greater distances from the periphery of colonies on thick hydrogels compared to thin hydrogels. Our data suggest that by acting collectively, cells mechanosense rigid materials beneath elastic hydrogels at greater depths than individual cells. This raises the possibility that the collective action of cells in colonies or sheets may allow cells to sense structures of differing material properties at comparatively large distances.
Keywords
Cell Line, Tumor, Elasticity, Extracellular Matrix/metabolism, Humans, Mechanotransduction, Cellular, Models, Biological, Pseudopodia/metabolism, Single-Cell Analysis, rho-Associated Kinases/metabolism
Pubmed
Web of science
Open Access
Yes
Create date
12/01/2024 10:14
Last modification date
13/01/2024 7:10