论文标题

在光学诱捕测定中,通过捕获粘合电动机对货物运输的理论分析

Theoretical analysis of cargo transport by catch bonded motors in optical trapping assays

论文作者

Sundararajan, Naren, Guha, Sougata, Muhuri, Sudipto, Mitra, Mithun K.

论文摘要

Dynein电动机表现出捕获的键合,其中微管丝中的电动机的未连接速率随着相对负载的增加而降低。这种捕捞键对动力蛋白驱动货物的运输特性的含义尚未完全理解。在这种情况下,光学诱捕测定构成了准确测量分子运动蛋白产生的力的重要手段。我们使用理论和随机模拟调查了通过谐波电位的捕获键合的动力蛋白分子电动机运输的货物的运输特性,这些发动机在谐波电位上进行了模拟,这模仿了货物在光学陷阱中所经历的可变力。我们估计了第一次通道时间的生物学相关度量 - 货物与微管和脱离力保持结合的时间 - 货物从微管中解开微管的力,同时使用二维和一维力平衡框架。我们的结果表明,即使对于由单个电动机运输的货物,捕获键合可能会根据力量表发挥作用,这标志着捕获键的发作。通过与单个动力蛋白驱动转运上的实验测量值进行比较,我们估计了该捕获键量尺度的现实界限。一般而言,捕获粘结会导致持续运动的增加,并且还可以产生第一通道时间的非单调行为。对于由多个电动机运输的货物,由于捕获粘结而引起的紧急集体效应可能导致非平凡的重新进入现象,其中平均第一次通过时间和脱离力表现出非单调行为,这是摊位力和运动速度的函数。

Dynein motors exhibit catch bonding, where the unbinding rate of the motors from microtubule filaments decreases with increasing opposing load. The implications of this catch bond on the transport properties of dynein-driven cargo are yet to be fully understood. In this context, optical trapping assays constitute an important means of accurately measuring the forces generated by molecular motor proteins. We investigate, using theory and stochastic simulations, the transport properties of cargo transported by catch bonded dynein molecular motors - both singly and in teams - in a harmonic potential, which mimics the variable force experienced by cargo in an optical trap. We estimate the biologically relevant measures of first passage time - the time during which the cargo remains bound to the microtubule and detachment force -the force at which the cargo unbinds from the microtubule, using both two-dimensional and one-dimensional force balance frameworks. Our results suggest that even for cargo transported by a single motor, catch bonding may play a role depending on the force scale which marks the onset of the catch bond. By comparing with experimental measurements on single dynein-driven transport, we estimate realistic bounds of this catch bond force scale. Generically, catch bonding results in increased persistent motion, and can also generate non-monotonic behaviour of first passage times. For cargo transported by multiple motors, emergent collective effects due to catch bonding can result in non-trivial re-entrant phenomena wherein average first passage times and detachment forces exhibit non-monotonic behaviour as a function of the stall force and the motor velocity.

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