Microenvironmental stiffness mediates cytoskeleton re-organization in chondrocytes through laminin-FAK mechanotransduction  

作　　者：Chenchen Zhou Mengmeng Duan Daimo Guo Xinmei Du Demao Zhang Jing Xie 

机构地区：[1]State Key Laboratory of Oral Diseases&National Clinical Research Center for Oral Diseases,West China Hospital of Stomatology,Sichuan University,Chengdu,China [2]Department of Cariology and Endodontics,West China Hospital of Stomatology,Sichuan University,Chengdu,China

出　　处：《International Journal of Oral Science》2022年第2期182-191,共10页国际口腔科学杂志（英文版）

基　　金：supported by the National Natural Science Foundation of China(81771047 to Jing Xie,81901040,82171001 to C.Z.);by the Young Elite Scientist Sponsorship Program by CAST(2020QNR001)。

摘　　要：Microenvironmental biophysical factors play a fundamental role in controlling cell behaviors including cell morphology,proliferation,adhesion and differentiation,and even determining the cell fate.Cells are able to actively sense the surrounding mechanical microenvironment and change their cellular morphology to adapt to it.Although cell morphological changes have been considered to be the first and most important step in the interaction between cells and their mechanical microenvironment,their regulatory network is not completely clear.In the current study,we generated silicon-based elastomer polydimethylsiloxane(PDMS)substrates with stiff(15:1,PDMS elastomer vs.curing agent)and soft(45:1)stiffnesses,which showed the Young’s moduli of~450 k Pa and 46 kPa,respectively,and elucidated a new path in cytoskeleton re-organization in chondrocytes in response to changed substrate stiffnesses by characterizing the axis shift from the secreted extracellular protein lamininβ1,focal adhesion complex protein FAK to microfilament bundling.We first showed the cellular cytoskeleton changes in chondrocytes by characterizing the cell spreading area and cellular synapses.We then found the changes of secreted extracellular linkage protein,lamininβ1,and focal adhesion complex protein,FAK,in chondrocytes in response to different substrate stiffnesses.These two proteins were shown to be directly interacted by Co-IP and colocalization.We next showed that impact of FAK on the cytoskeleton organization by showing the changes of microfilament bundles and found the potential intermediate regulators.Taking together,this modulation axis of lamininβ1-FAK-microfilament could enlarge our understanding about the interdependence among mechanosensing,mechanotransduction,and cytoskeleton re-organization.

关 键 词：LAMININ mec STIFFNESS 

分 类 号：R329.2[医药卫生—人体解剖和组织胚胎学]