title: 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.
authors.affiliation: 1] Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, 313 Ferst Drive, Atlanta, Georgia 30332, USA [2] Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, 315 Ferst Drive, Atlanta, Georgia 30332, USA [3].
authors.forename: Vincent F
authors.initials: VF
authors.lastname: Fiore
authors.affiliation: 1] Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, 313 Ferst Drive, Atlanta, Georgia 30332, USA [2] Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, 315 Ferst Drive, Atlanta, Georgia 30332, USA [3].
authors.forename: Lining
authors.initials: L
authors.lastname: Ju
authors.affiliation: 1] Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, 315 Ferst Drive, Atlanta, Georgia 30332, USA [2] Woodruff School of Mechanical Engineering, Georgia Institute of Technology, 801 Ferst Drive, Atlanta, Georgia 30332, USA.
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Chen
authors.affiliation: 1] Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, 313 Ferst Drive, Atlanta, Georgia 30332, USA [2] Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, 315 Ferst Drive, Atlanta, Georgia 30332, USA [3] Woodruff School of Mechanical Engineering, Georgia Institute of Technology, 801 Ferst Drive, Atlanta, Georgia 30332, USA.
authors.forename: Cheng
authors.initials: C
authors.lastname: Zhu
authors.affiliation: 1] Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, 313 Ferst Drive, Atlanta, Georgia 30332, USA [2] Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, 315 Ferst Drive, Atlanta, Georgia 30332, USA.
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Barker
mesh_terms: D001696:Biomechanical Phenomena; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D015870:Gene Expression; D006801:Humans; D039081:Integrin alpha5beta1 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D019012:Integrin beta1 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D020014:K562 Cells; D040542:Mechanotransduction, Cellular; D011485:Protein Binding; D017510:Protein Folding; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D053671:Syndecan-4 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D013718:Tensile Strength; D018800:Thy-1 Antigens / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D039081:Integrin alpha5beta1; D019012:Integrin beta1; D011994:Recombinant Proteins; D053671:Syndecan-4; D018800:Thy-1 Antigens