Dataset Information

Epithelial Monolayers Coalesce on a Viscoelastic Substrate through Redistribution of Vinculin.

ABSTRACT: The mechanical properties of the microenvironment play a large role in influencing cellular behavior. In particular, the tradeoff between substrate viscosity and elasticity on collective cell migration by adherent cells is highly physiologically relevant, but remains poorly understood. To investigate the specific effects of viscous substrates, we plated epithelial monolayers onto polydimethylsiloxane substrata with a range of viscosities and elasticities. We found that on viscoelastic substrates the monolayers underwent rapid and coordinated movement to generate cell-free areas. To understand the molecular mechanism of this coordinated movement, we imaged various structural and signaling proteins at cell-cell and cell-matrix junctions. Through quantitative image analysis of monolayer disruption and subcellular protein redistribution, we show that the mechanosensor protein, vinculin, is necessary and sufficient for this viscous response, during which it is lost from focal adhesions and recruited by the cadherin complex to intercellular junctions. In addition, the viscous response is dependent upon and enhanced by actomyosin contractility. Our results implicate vinculin translocation in a molecular switching mechanism that senses substrate viscoelasticity and associates with actomyosin contractility.

SUBMITTER: Zheng JY

PROVIDER: S-EPMC5627150 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Epithelial Monolayers Coalesce on a Viscoelastic Substrate through Redistribution of Vinculin.

Zheng Ji Yun JY Han Siew Ping SP Chiu Yi-Jen YJ Yip Ai Kia AK Boichat Nicolas N Zhu Shi Wen SW Zhong Jun J Matsudaira Paul P

Biophysical journal 20170824 7

The mechanical properties of the microenvironment play a large role in influencing cellular behavior. In particular, the tradeoff between substrate viscosity and elasticity on collective cell migration by adherent cells is highly physiologically relevant, but remains poorly understood. To investigate the specific effects of viscous substrates, we plated epithelial monolayers onto polydimethylsiloxane substrata with a range of viscosities and elasticities. We found that on viscoelastic substrates ...[more]

PMID: 28844472

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Project description:PurposeThe importance of mechanical forces and microenvironment in guiding cellular behavior has been widely accepted. Together with the extracellular matrix (ECM), epithelial cells form a highly connected mechanical system subjected to various mechanical cues from their environment, such as ECM stiffness, and tensile and compressive forces. ECM stiffness has been linked to many pathologies, including tumor formation. However, our understanding of the effect of ECM stiffness and its heterogeneities on rapid force transduction in multicellular systems has not been fully addressed.MethodsWe used experimental and computational methods. Epithelial cells were cultured on elastic hydrogels with fluorescent nanoparticles. Single cells were moved by a micromanipulator, and epithelium and substrate deformation were recorded. We developed a computational model to replicate our experiments and quantify the force distribution in the epithelium. Our model further enabled simulations with local stiffness gradients.ResultsWe found that substrate stiffness affects the force transduction and the cellular deformation following an external force. Also, our results indicate that the heterogeneities, e.g., gradients, in the stiffness can substantially influence the strain redistribution in the cell monolayers. Furthermore, we found that the cells' apico-basal elasticity provides a level of mechanical isolation between the apical cell-cell junctions and the basal focal adhesions.ConclusionsOur simulation results show that increased ECM stiffness, e.g., due to a tumor, can mechanically isolate cells and modulate rapid mechanical signaling between cells over distances. Furthermore, the developed model has the potential to facilitate future studies on the interactions between epithelial monolayers and elastic substrates.Supplementary informationThe online version of this article (10.1007/s12195-023-00772-0) contains supplementary material, which is available to authorized users.

Dataset Information

Epithelial Monolayers Coalesce on a Viscoelastic Substrate through Redistribution of Vinculin.

Publications

Epithelial Monolayers Coalesce on a Viscoelastic Substrate through Redistribution of Vinculin.

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