Integrins outside focal adhesions transmit tensions during stable cell adhesion.

Yongliang Wang,Xuefeng Wang

doi:10.1038/srep36959

Abstract

Integrins coupled with other proteins form protein complexes named focal adhesions (FA) which are considered as the primary sites for cellular forces transduction during cell stable adhesion. Cell traction forces transmitted by FAs and integrin tensions inside FAs have been extensively studied. However, it remains unknown whether integrins outside FAs can transmit tension, and if so, what is the tension range. We previously developed a tension sensor named tension gauge tether (TGT). To calibrate integrin tensions outside FAs, here we applied multiplex TGT (mTGT) to simultaneously monitor integrin tensions at separate levels. mTGT unambiguously revealed that integrins outside FAs also transmit tension after FA formation. These tensions are mainly located in the range of 43 ~ 54 pN which is lower than integrin tensions inside FAs. Integrin tensions both inside and outside FAs substantially contribute to bulk cellular forces and they respond independently to actin and myosin II inhibition, serum deprivation and microtubule inhibition, indicating their different tension sources and independent dynamics. Our work identified integrin tensions outside FAs and calibrated the tension range for the first time. We also demonstrated that mTGT is a valuable tool to monitor integrin tension profile in a broad detection range of 10 ~ 60 pN.

Highlights

Integrins are the major membrane proteins that establish physical linkage and mediate mechanical signaling between cells and the matrix[1]
We developed multiplex TGT (mTGT) to co-map multiple levels of integrin tensions and explored the integrin tensions outside focal adhesions (FA). mTGT overcomes the obstacle that the tension gauge tether (TGT) required for measuring integrin tensions at a low level may not support cell adhesion
On an mTGT surface, cells stably adhered with FA formation and integrin tensions were simultaneously mapped at different levels. mTGT revealed that integrins outside FAs transmit tensions which were mainly located in the range of 43 ~ 54 pN

Summary

Introduction

Integrins are the major membrane proteins that establish physical linkage and mediate mechanical signaling between cells and the matrix[1]. A series of surface-tethered molecular tension sensors have been developed to measure and map integrin tensions in real-time[14,15,16,17,18,19]. These techniques provide quantitative approaches to study integrin tensions, and revealed new insights to integrin signaling pathways. These two types of tensions are active in different tension ranges and respond independently to the inhibition of myosin, actin and microtubule, and serum deprivation This discovery provides a more complete view about how integrins transmit cellular forces during stable cell adhesion

Methods

Results

Conclusion