Research Papers

Coupling of Bond Breaking With State Transition Leads to High Apparent Detachment Rates of a Single Myosin

[+] Author and Article Information
C. Dong

Department of Engineering Mechanics,
Zhejiang University,
Hangzhou 310027, China

B. Chen

Department of Engineering Mechanics,
Zhejiang University,
Hangzhou 310027, China
e-mail: chenb6@zju.edu.cn

1Corresponding author.

Contributed by the Applied Mechanics Division of ASME for publication in the JOURNAL OF APPLIED MECHANICS. Manuscript received January 31, 2016; final manuscript received February 24, 2016; published online March 11, 2016. Editor: Yonggang Huang.

J. Appl. Mech 83(5), 051011 (Mar 11, 2016) (7 pages) Paper No: JAM-16-1061; doi: 10.1115/1.4032860 History: Received January 31, 2016; Revised February 24, 2016

Quantifying interactions between motors and filaments is important for the understanding of intriguing emergent behaviors of motor–filament systems, which play critical roles in various biological processes. Recently, unusually high detachment rates of a myosin from actin were obtained with a force spectroscopy technique of an unprecedented spatial–temporal resolution. Here, we suggest that these high apparent detachment rates may be due to the inherent coupling between bond breaking and state transition, which can be common in protein–protein interactions. Based on a kinetic model for the chemomechanical cycle of single myosin, rates of bond breaking between myosin and actin at different nucleotide states are systematically calculated. These quantitative results indicate that myosins may adopt much higher transition rates than bond breaking rates at different nucleotide states under physiological conditions when applied forces are relatively low. This work also indicates that accurate biophysical models considering both protein unbinding dynamics and protein state transitions are required in order to properly interpret the experimental data when the ultrafast force-clamp spectroscopy technique is employed to study, for example, the DNA–protein interactions.

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Grahic Jump Location
Fig. 1

(a) A schematic digram illustrating the application of a constant force, f, to a myosin motor, which is just bound to actin. (b) State map within a chemomechanical cycle of a single myosin II.

Grahic Jump Location
Fig. 2

(a) The dependence of k1 on ATP concentration [ATP] [26]. Note that k1 is the apparent detachment rate of myosin from actin after ATP binding, which can linearly increase with ATP concentration. (b) The dependence of r30 on force based on the analysis of the experimental data [26]. Note that r30 is the bond breaking rate of myosin at State AM. The increase of r30 with force indicates it as a slip bond.

Grahic Jump Location
Fig. 3

(a) The dependence of k2 on f when f  <  6 pN. The data points were extracted from Capitanio et al. [26]. (b) The dependence of r10 on f when f  <  6 pN, which is fitted with a Bell's function [27] being represented as a line. The data points are calculated in the current work, where no numerical simulation is involved. (c) The dependence of k3 on f when f  <  6 pN. The data points were extracted from Capitanio et al. [26]. (d) The dependence of k2 or k3 on f when f  ≥  6 pN. The data points were extracted from Capitanio et al. [26].

Grahic Jump Location
Fig. 4

State map of a myosin detaching from actin at high forces (f  >  6 pN)



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