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Author Notes:

Correspondence: larry.mcintire@bme.gatech.edu or cheng.zhu@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.

Acknowledgements: We thank V. M. Fowler for reagents and F. Kong for help with AFM.

Disclosures: The authors declare no conflict of interest.


Research Funding:

This work was supported by National Institutes of Health Grants HL18672 and HL70537 (to L.V.M.); HL091020, HL093723, AI077343, and AI044902 (to C.Z.); AR48615 (to S.O.); and DC8803 (to P.A.R.); and by National Natural Science Foundation of China Grants 31070827, 31222022, and 81161120424 (to J.L.).

The computational resources for the SMD simulations were provided by National Science Foundation Teragrid Large Resource Allocations Committee Grant MCA08X014 (to C.Z.) and by the Supercomputing Center of Chinese Academy of Sciences and National Supercomputing Center Tianjin Center (J.L.).


  • Science & Technology
  • Multidisciplinary Sciences
  • Science & Technology - Other Topics
  • single-molecule force spectroscopy
  • mechanotransduction
  • mechanosensing
  • nemaline myopathy
  • Adhesive contacts
  • Structural basis
  • Stress fibers
  • Cell
  • Tension
  • Filament
  • Dynamics
  • Integrin
  • Mechanosensors
  • Organization

Actin depolymerization under force is governed by lysine 113:glutamic acid 195-mediated catch-slip bonds


Journal Title:



Volume 110, Number 13


, Pages 5022-5027

Type of Work:

Article | Final Publisher PDF


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-clampexperiments, 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 catchslip bonds, which may provide a mechanoregulatory mechanism to control cell functions by regulating the depolymerization kinetics of force-bearing actin filaments throughout the cytoskeleton. © PNAS 2013.

Copyright information:

© 2013 National Academy of Sciences.

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