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Dynamic catch of a Thy-1–α5β1+syndecan-4 trimolecular complex

Vincent F. Fiore, Lining Ju, Yunfeng Chen, Cheng Zhu () and Thomas H. Barker ()
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Vincent F. Fiore: Georgia Institute of Technology
Lining Ju: Georgia Institute of Technology
Yunfeng Chen: Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology
Cheng Zhu: Georgia Institute of Technology
Thomas H. Barker: Georgia Institute of Technology

Nature Communications, 2014, vol. 5, issue 1, 1-12

Abstract: Abstract Cancer cell adhesion to the vascular endothelium is a critical step of tumour metastasis. Endothelial surface molecule Thy-1 (CD90) is implicated in the metastatic process through its interactions with integrins and syndecans. However, how Thy-1 supports cell–cell adhesion in a dynamic mechanical environment is not known. Here we show that Thy-1 supports β1 integrin- and syndecan-4 (Syn4)-mediated contractility-dependent mechanosignalling of melanoma cells. At the single-molecule level, Thy-1 is capable of independently binding α5β1 integrin and syndecan-4 (Syn4) receptors. However, in the presence of both α5β1 and Syn4, the two receptors bind cooperatively to Thy-1, to form a trimolecular complex. This trimolecular complex displays a unique phenomenon we coin ‘dynamic catch’, characterized by abrupt bond stiffening followed by the formation of catch bonds, where force prolongs the bond lifetime. Thus, we reveal a new class of trimolecular interactions where force strengthens the synergistic binding of two co-receptors and modulates downstream mechanosignalling.

Date: 2014
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms5886

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DOI: 10.1038/ncomms5886

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