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Author Notes:

Correspondence and requests for materials should be addressed to C.Z. (email: cheng.zhu@bme.gatech.edu) or L.V.M. (email: larry.mcintire@bme.gatech.edu).

C.-Y.L. initiated the project.

C.-Y.L., J.L., S.G.E, S.O., P.A.R., C.Z and L.V.M. designed the research.

C.-Y.L. conducted the AFM experiments and analyzed data.

J.L. performed the SMD simulations.

K.-K.W. and M.M. generated and purified the yeast actin mutants.

C.-Y.L., J.L., S.G.E., S.O., S.C., P.A.R., C.Z. and L.V.M. wrote the paper.

We thank V.M. Fowler, H.N. Higgs and D.R. Kovar for kindly providing us with reagents. W also thank Dr. Hyun-Jung Lee for supplying some of the data presented in Figure S2.

The authors declare no competing financial interests.


Research Funding:

This work was supported by NIH grants (HL18672, HL70537 to L.V.M.; AI044902, HL132019to C.Z.; AR48615 to S.O.; GM33689 to P.A.R.) and Army Research Office grant W911NF-16-1-0257 to C.Z.

The computational resources were provided by National Supercomputing Center Tianjin Center under the support by the National Basic Research Program of China (2014CB910202 to J.L.).


  • Science & Technology
  • Multidisciplinary Sciences
  • CELL
  • MDIA1
  • Biophysical chemistry
  • Single-molecule biophysics

Regulation of actin catch-slip bonds with a RhoA-formin module


Journal Title:

Scientific Reports


Volume 6


, Pages 35058-35058

Type of Work:

Article | Final Publisher PDF


The dynamic turnover of the actin cytoskeleton is regulated cooperatively by force and biochemical signaling. We previously demonstrated that actin depolymerization under force is governed by catch-slip bonds mediated by force-induced K113:E195 salt-bridges. Yet, the biochemical regulation as well as the functional significance of actin catch bonds has not been elucidated. Using AFM force-clamp experiments, we show that formin controlled by RhoA switches the actin catch-slip bonds to slip-only bonds. SMD simulations reveal that the force does not induce the K113:E195 interaction when formin binds to actin K118 and E117 residues located at the helical segment extending to K113. Actin catch-slip bonds are suppressed by single residue replacements K113E and E195K that interrupt the force-induced K113:E195 interaction; and this suppression is rescued by a K113E/E195K double mutant (E/K) restoring the interaction in the opposite orientation. These results support the biological significance of actin catch bonds, as they corroborate reported observations that RhoA and formin switch force-induced actin cytoskeleton alignment and that either K113E or E195K induces yeast cell growth defects rescued by E/K. Our study demonstrates how the mechano-regulation of actin dynamics is modulated by biochemical signaling molecules, and suggests that actin catch bonds may be important in cell functions.

Copyright information:

© The Author(s) 2016.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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