Load-dependent kinetics of force production by smooth muscle myosin measured with optical tweezers

被引:269
作者
Veigel, C
Molloy, JE
Schmitz, S
Kendrick-Jones, J
机构
[1] Natl Inst Med Res, Div Phys Biochem, London NW7 1AA, England
[2] MRC, Mol Biol Lab, Cambridge CB2 2QH, England
基金
英国医学研究理事会; 英国生物技术与生命科学研究理事会;
关键词
D O I
10.1038/ncb1060
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Muscle contraction is driven by the cyclical interaction of myosin with actin, coupled with ATP hydrolysis. Myosin attaches to actin, forming a crossbridge that produces force and movement as it tilts(1) or rocks into subsequent bound states(2) before finally detaching. It has been hypothesized that the kinetics of one or more of these mechanical transitions are dependent on load, allowing muscle to shorten quickly under low load, but to sustain tension economically, with slowly cycling crossbridges under high load conditions(2-6). The idea that muscle biochemistry depends on mechanical output is termed the 'Fenn effect'. However, the molecular details of how load affects the kinetics of a single crossbridge are unknown. Here, we describe a new technique based on optical tweezers to rapidly apply force to a single smooth muscle myosin crossbridge. The crossbridge produced movement in two phases that contribute 4 nm + 2 nm of displacement. Duration of the first phase depended in an exponential manner on the amplitude of applied load. Duration of the second phase was much less affected by load, but was significantly shorter at high ATP concentration. The effect of load on the lifetime of the bound crossbridge is to prolong binding when load is high, but to accelerate release when load is low or negative.
引用
收藏
页码:980 / 986
页数:7
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