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Spatial Proliferation of Epithelial Cells Is Regulated by E-Cadherin Force.

Abstract：

:Cell proliferation and contact inhibition play a major role in maintaining epithelial cell homeostasis. Prior experiments have shown that externally applied forces, such as stretch, result in increased proliferation in an E-cadherin force-dependent manner. In this study, the spatial regulation of cell proliferation in large epithelial colonies was examined. Surprisingly, cells at the center of the colony still had increased proliferation as compared to cells in confluent monolayers. E-cadherin forces were found to be elevated for both cells at the edge and center of these larger colonies when compared to confluent monolayers. To determine if high levels of E-cadherin force were necessary to induce proliferation at the center of the colony, a lower-force mutant of E-cadherin was developed. Cells with lower E-cadherin force had significantly reduced proliferation for cells at the center of the colony but minimal differences for cells at the edges of the colony. Similarly, increasing substrate stiffness was found to increase E-cadherin force and increase the proliferation rate across the colony. Taken together, these results show that forces through cell-cell junctions regulate proliferation across large groups of epithelial cells. In addition, an important finding of this study is that junction forces are dynamic and modulate cellular function even in the absence of externally applied loads.

journal_name

Biophys J

journal_title

Biophysical journal

authors

Mohan A,Schlue KT,Kniffin AF,Mayer CR,Duke AA,Narayanan V,Arsenovic PT,Bathula K,Danielsson BE,Dumbali SP,Maruthamuthu V,Conway DE

doi

10.1016/j.bpj.2018.07.030

subject

Has Abstract

pub_date

2018-09-04 00:00:00

pages

853-864

issue

5

eissn

0006-3495

issn

1542-0086

pii

S0006-3495(18)30917-2

journal_volume

115

pub_type

杂志文章

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