Mechanism of muscle contraction based on stochastic properties of single actomyosin motors observed in vitro

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概要

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• We have previously measured the process of displacement generation by a single head of muscle myosin (S1) using scanning probe nanometry. Given that the myosin head was rigidly attached to a fairly large scanning probe, it was assumed to stably interact with an underlying actin filament without diffusing away as would be the case in muscle. The myosin head has been shown to step back and forth stochastically along an actin filament with actin monomer repeats of 5.5 nm and to produce a net movement in the forward direction. The myosin head underwent 5 forward steps to produce a maximum displacement of 30 nm per ATP at low load (<1 pN). Here, we measured the steps over a wide range of forces up to 4 pN. The size of the steps (~5.5 nm) did not change as the load increased whereas the number of steps per displacement and the stepping rate both decreased. The rate of the 5.5-nm steps at various force levels produced a force-velocity curve of individual actomyosin motors. The force-velocity curve from the individual myosin heads was comparable to that reported in muscle, suggesting that the fundamental mechanical properties in muscle are basically due to the intrinsic stochastic nature of individual actomyosin motors. In order to explain multiple stochastic steps, we propose a model arguing that the thermally-driven step of a myosin head is biased in the forward direction by a potential slope along the actin helical pitch resulting from steric compatibility between the binding sites of actin and a myosin head. Furthermore, computer simulations show that multiple cooperating heads undergoing stochastic steps generate a long (>60 nm) sliding distance per ATP between actin and myosin filaments, i.e., the movement is loosely coupled to the ATPase cycle as observed in muscle.

著者

• Tokunaga Makio

  Structural Biology Center, National Institute of Genetics

• Tokunaga Makio

  Structural Biology Center National Institute Of Genetics:the Graduated University For Advanced Studi

• Yanagida Toshio

  Single Molecule Process Project Icorp Jst

• Yanagida Toshio

  Single Molecule Processes Project, JST

• Esaki Seiji

  Department of Physiology & Biosignaling, Osaka University Medical School

• Hikikoshi Iwane

  Department of Physiology & Biosignaling, Osaka University Medical School

• Kitamura Kazuo

  Single Molecule Processes Project, JST

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