Mechanotransduction of matrix stiffness in regulation of focal adhesion size and number: Reciprocal regulation of caveolin-1 and β1 integrin

Yi Chun Yeh, Jin Ying Ling, Wan Chun Chen, Hsi Hui Lin, Ming Jer Tang

Research output: Contribution to journalArticlepeer-review

56 Citations (Scopus)

Abstract

Focal adhesion (FA) assembly, mediated by integrin activation, responds to matrix stiffness; however, the underlying mechanisms are unclear. Here, we showed that β1 integrin and caveolin-1 (Cav1) levels were decreased with declining matrix stiffness. Soft matrix selectively downregulated β1 integrin by endocytosis and subsequent lysosomal degradation. Disruption of lipid rafts with methyl-β-cyclodextrin or nystatin, or knockdown of Cav1 by siRNA decreased cell spreading, FA assembly, and β1 integrin protein levels in cells cultured on stiff matrix. Overexpression of Cav1, particularly the phospho-mimetic mutant Cav1-Y14D, averted soft matrix-induced decreases in β1 integrin protein levels, cell spreading, and FA assembly in NMuMG cells. Interestingly, overexpression of an auto-clustering β1 integrin hindered soft matrix-induced reduction of Cav1 and cell spreading, which suggests a reciprocal regulation between β1 integrin and Cav1. Finally, co-expression of this auto-clustering β1 integrin and Cav1-Y14D synergistically enhanced cell spreading, and FA assembly in HEK293T cells cultured on either stiff (> G Pa) or soft (0.2 kPa) matrices. Collectively, these results suggest that matrix stiffness governs the expression of β1 integrin and Cav1, which reciprocally control each other, and subsequently determine FA assembly and turnover.

Original languageEnglish
Article number15008
JournalScientific reports
Volume7
Issue number1
DOIs
Publication statusPublished - 2017 Dec 1

All Science Journal Classification (ASJC) codes

  • General

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