Muons penetrate much further than X-rays, they do essentially zero damage, and they are provided for free by the cosmos.
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Edited by Paul A. Janmey, University of Pennsylvania, Philadelphia, PA, and accepted by the Editorial Board February 11, 2013 (received for review October 24, 2012)
Abstract
As a key element in the cytoskeleton, actin filaments are highly dynamic structures that constantly sustain forces. However, the fundamental question of how force regulates actin dynamics is unclear. Using atomic force microscopy force-clamp experiments, we show that tensile force regulates G-actin/G-actin and G-actin/F-actin dissociation kinetics by prolonging bond lifetimes (catch bonds) at a low force range and by shortening bond lifetimes (slip bonds) beyond a threshold. Steered molecular dynamics simulations reveal force-induced formation of new interactions that include a lysine 113(K113):glutamic acid 195 (E195) salt bridge between actin subunits, thus suggesting a molecular basis for actin catch-slip bonds. This structural mechanism is supported by the suppression of the catch bonds by the single-residue replacements K113 to serine (K113S) and E195 to serine (E195S) on yeast actin. These results demonstrate and provide a structural explanation for actin catch-slip bonds, which may provide a mechanoregulatory mechanism to control cell functions by regulating the depolymerization kinetics of force-bearing actin filaments throughout the cytoskeleton.
Footnotes
↵1C.-y.L. and J.L. contributed equally to this work.
- ↵2To whom correspondence may be addressed. E-mail: larry.mcintire{at}bme.gatech.edu or cheng.zhu{at}bme.gatech.edu.
Author contributions: C.-y.L. initiated the project; C.-y.L., S.G.E., S.O., P.A.R., C.Z., and L.V.M. designed research; C.-y.L. conducted the AFM experiments; J.L. performed the SMD simulations; K.-k.W. and M.M. generated and purified the yeast actin mutants; K.-k.W., M.M., and P.A.R. contributed new reagents/analytic tools; C.-y.L. and J.L. analyzed data; and C.-y.L., J.L., S.G.E., S.O., S.C., P.A.R., C.Z., and L.V.M. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission. P.A.J. is a guest editor invited by the Editorial Board.
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1218407110/-/DCSupplemental.
Actin catch-slip bonds
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