Defining single molecular forces required to activate integrin and notch signaling

X Wang, T Ha - Science, 2013 - science.org
Science, 2013science.org
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 …
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.
AAAS