title: Defining single molecular forces required to activate integrin and notch signaling.
abstract: Cell-cell and cell-matrix mechanical interactions through membrane receptors direct a wide range of cellular functions and orchestrate the development of multicellular organisms. To define the single molecular forces required to activate signaling through a ligand-receptor bond, we developed the tension gauge tether (TGT) approach in which the ligand is immobilized to a surface through a rupturable tether before receptor engagement. TGT serves as an autonomous gauge to restrict the receptor-ligand tension. Using a range of tethers with tunable tension tolerances, we show that cells apply a universal peak tension of about 40 piconewtons (pN) to single integrin-ligand bonds during initial adhesion. We find that less than 12 pN is required to activate Notch receptors. TGT can also provide a defined molecular mechanical cue to regulate cellular functions.
authors.affiliation: Department of Physics, Center for the Physics of Living Cells and Institute for Genomic Biology University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Wang
authors.forename: Taekjip
authors.initials: T
authors.lastname: Ha
mesh_terms: D000818:Animals; D016466:CHO Cells; D002448:Cell Adhesion; D002450:Cell Communication; D006224:Cricetinae; D003412:Cricetulus; D004247:DNA / Q000737:chemistry; D057809:HEK293 Cells; D006801:Humans; D016023:Integrins / Q000819:agonists*; D008024:Ligands; D040542:Mechanotransduction, Cellular; D051379:Mice; D041681:NIH 3T3 Cells; D051880:Receptors, Notch / Q000819:agonists*; D033081:Shear Strength; D013499:Surface Properties
chemical_list: D016023:Integrins; D008024:Ligands; D051880:Receptors, Notch; D004247:DNA