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

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.
AuthorsVincent F Fiore, Lining Ju, Yunfeng Chen, Cheng Zhu, Thomas H Barker
JournalNature communications (Nat Commun) Vol. 5 Pg. 4886 (Sep 12 2014) ISSN: 2041-1723 [Electronic] England
PMID25216363 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
Chemical References
  • Integrin alpha5beta1
  • Integrin beta1
  • Recombinant Proteins
  • Syndecan-4
  • Thy-1 Antigens
Topics
  • Biomechanical Phenomena
  • Cell Adhesion
  • Cell Line, Tumor
  • Gene Expression
  • Humans
  • Integrin alpha5beta1 (chemistry, genetics, metabolism)
  • Integrin beta1 (chemistry, genetics, metabolism)
  • K562 Cells
  • Mechanotransduction, Cellular
  • Protein Binding
  • Protein Folding
  • Recombinant Proteins (chemistry, genetics, metabolism)
  • Syndecan-4 (chemistry, genetics, metabolism)
  • Tensile Strength
  • Thy-1 Antigens (chemistry, genetics, metabolism)

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