title: Two-piconewton slip bond between fibronectin and the cytoskeleton depends on talin.
abstract: Mechanical forces on matrix-integrin-cytoskeleton linkages are crucial for cell viability, morphology and organ function. The production of force depends on the molecular connections from extracellular-matrix-integrin complexes to the cytoskeleton. The minimal matrix complex causing integrin-cytoskeleton connections is a trimer of fibronectin's integrin-binding domain FNIII7-10 (ref. 4). Here we report a specific, molecular slip bond that was broken repeatedly by a force of 2 pN at the cellular loading rate of 60 nm x s(-1); this occurred with single trimer beads but not with monomer. Talin1, which binds to both integrins and actin filaments in vitro, is required for the 2-pN slip bond and rapid cytoskeleton binding. Further, inhibition of fibronectin binding to alpha(v)beta3 and deletion of beta3 markedly decreases the 2-pN force peak. We suggest that talin1 initially forms a molecular slip bond between closely packed fibronectin-integrin complexes and the actin cytoskeleton, which can apply a low level of force to fibronectin until many bonds form or a signal is received to activate a force response.
authors.affiliation: Department of Biological Sciences, Columbia University, 1212 Amsterdam Avenue, New York, New York 11027, USA.
authors.forename: Guoying
authors.initials: G
authors.lastname: Jiang
authors.forename: Grégory
authors.initials: G
authors.lastname: Giannone
authors.forename: David R
authors.initials: DR
authors.lastname: Critchley
authors.forename: Emiko
authors.initials: E
authors.lastname: Fukumoto
authors.forename: Michael P
authors.initials: MP
authors.lastname: Sheetz
mesh_terms: D016475:3T3 Cells; D000199:Actins / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D003599:Cytoskeleton / Q000378:metabolism*; D005353:Fibronectins / Q000378:metabolism*; D039302:Integrin alphaVbeta3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D039661:Integrin beta3 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D011485:Protein Binding; D016608:Talin / Q000235:genetics / Q000378:metabolism*
chemical_list: D000199:Actins; D005353:Fibronectins; D039302:Integrin alphaVbeta3; D039661:Integrin beta3; D016608:Talin