Department of Bioengineering, Rice University, Houston, Texas, USA.
Biophys J. 2011 Jul 20;101(2):386-95. doi: 10.1016/j.bpj.2011.05.067.
Subcellular cargos are often transported by teams of processive molecular motors, which raises questions regarding the role of motor cooperation in intracellular transport. Although our ability to characterize the transport behaviors of multiple-motor systems has improved substantially, many aspects of multiple-motor dynamics are poorly understood. This work describes a transition rate model that predicts the load-dependent transport behaviors of multiple-motor complexes from detailed measurements of a single motor's elastic and mechanochemical properties. Transition rates are parameterized via analyses of single-motor stepping behaviors, load-rate-dependent motor-filament detachment kinetics, and strain-induced stiffening of motor-cargo linkages. The model reproduces key signatures found in optical trapping studies of structurally defined complexes composed of two kinesin motors, and predicts that multiple kinesins generally have difficulties in cooperating together. Although such behavior is influenced by the spatiotemporal dependence of the applied load, it appears to be directly linked to the efficiency of kinesin's stepping mechanism, and other types of less efficient and weaker processive motors are predicted to cooperate more productively. Thus, the mechanochemical efficiencies of different motor types may determine how effectively they cooperate together, and hence how motor copy number contributes to the regulation of cargo motion.
细胞内的货物通常由一组连续运动的分子马达来运输,这就引发了关于马达协同作用在细胞内运输中的作用的问题。尽管我们已经大大提高了描述多马达系统运输行为的能力,但许多多马达动力学方面的问题仍然没有得到很好的理解。这项工作描述了一个转换速率模型,该模型可以根据单个马达的弹性和机械化学性质的详细测量结果,预测多马达复合物的负载依赖性运输行为。转换速率通过对单马达步进行为、负载速率依赖性马达-纤维脱离动力学以及应变诱导的马达-货物连接变硬的分析进行参数化。该模型再现了在光学捕获研究中发现的由两个肌球蛋白马达组成的结构定义复合物的关键特征,并预测多个肌球蛋白通常很难协同工作。尽管这种行为受到施加负载的时空依赖性的影响,但它似乎与肌球蛋白步进机制的效率直接相关,并且预测其他类型效率较低且较弱的连续运动马达将更有效地协同工作。因此,不同类型的马达的机械化学效率可能决定了它们协同工作的有效性,因此马达拷贝数如何有助于货物运动的调节。