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Am J Physiol Cell Physiol 295: C1579-C1589, 2008. First published October 15, 2008; doi:10.1152/ajpcell.00223.2008
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EXTRACELLULAR MATRIX, CELL INTERACTIONS

Mechanosensing machinery for cells under low substratum rigidity

Wei-Chun Wei,1 Hsi-Hui Lin,2 Meng-Ru Shen,1,3 and Ming-Jer Tang1,2,3

1Institute of Basic Medical Sciences, 2Department of Physiology, and 3Center of Gene Regulation and Signal Transduction, National Cheng Kung University Medical College, Tainan, Taiwan

Submitted 23 April 2008 ; accepted in final form 4 October 2008

Mechanical stimuli are essential during development and tumorigenesis. However, how cells sense their physical environment under low rigidity is still unknown. Here we show that low rigidity of collagen gel downregulates β1-integrin activation, clustering, and focal adhesion kinase (FAK) Y397 phosphorylation, which is mediated by delayed raft formation. Moreover, overexpression of autoclustered β1-integrin (V737N), but not constitutively active β1-integrin (G429N), rescues FAKY397 phosphorylation level suppressed by low substratum rigidity. Using fluorescence resonance energy transfer to assess β1-integrin clustering, we have found that substratum rigidity between 58 and 386 Pa triggers β1-integrin clustering in a dose-dependent manner, which is highly dependent on actin filaments but not microtubules. Furthermore, augmentation of β1-integrin clustering enhances the interaction between β1-integrin, FAK, and talin. Our results indicate that contact with collagen fibrils is not sufficient for integrin activation. However, substratum rigidity is required for integrin clustering and activation. Together, our findings provide new insight into the mechanosensing machinery and the mode of action for epithelial cells in response to their physical environment under low rigidity.

focal adhesion kinase; β1-integrin activation; β1-integrin clustering; lipid raft; actin cytoskeleton


Address for reprint requests and other correspondence: M.-J. Tang, No. 1, University Rd., Dept. of Physiology, National Cheng Kung Univ. Medical College, Tainan 701, Taiwan (e-mail: mjtang1{at}mail.ncku.edu.tw)






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