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

Nat Commun. 2014 Sep 12;5:4886. doi: 10.1038/ncomms5886.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Biomechanical Phenomena
  • Cell Adhesion
  • Cell Line, Tumor
  • Gene Expression
  • Humans
  • Integrin alpha5beta1 / chemistry*
  • Integrin alpha5beta1 / genetics
  • Integrin alpha5beta1 / metabolism
  • Integrin beta1 / chemistry*
  • Integrin beta1 / genetics
  • Integrin beta1 / metabolism
  • K562 Cells
  • Mechanotransduction, Cellular
  • Protein Binding
  • Protein Folding
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Syndecan-4 / chemistry*
  • Syndecan-4 / genetics
  • Syndecan-4 / metabolism
  • Tensile Strength
  • Thy-1 Antigens / chemistry*
  • Thy-1 Antigens / genetics
  • Thy-1 Antigens / metabolism

Substances

  • Integrin alpha5beta1
  • Integrin beta1
  • Recombinant Proteins
  • Syndecan-4
  • Thy-1 Antigens