Logo image
Back
Collective Cell Behavior in Mechanosensing of Substrate Thickness
Journal article   Open access   Peer reviewed

Collective Cell Behavior in Mechanosensing of Substrate Thickness

Camelia G Tusan, Yu-Hin Man, Hoda Zarkoob, David A Johnston, Orestis G Andriotis, Philipp J Thurner, Shoufeng Yang, Edward A Sander, Eileen Gentleman, Bram G Sengers, …
Biophysical journal, Vol.114(11), pp.2743-2755
06/05/2018
DOI: 10.1016/j.bpj.2018.03.037
PMCID: PMC6027966
PMID: 29874622
url
https://doi.org/10.1016/j.bpj.2018.03.037View
Published (Version of record) Open Access

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.
 Elasticity Cell Line, Tumor Extracellular Matrix - metabolism Humans Mechanotransduction, Cellular Models, Biological Pseudopodia - metabolism rho-Associated Kinases - metabolism Single-Cell Analysis

Details

Metrics

7 Record Views
48 Times Cited - Web of Science
Logo image