微管-驱动蛋白输运系统的行走动力学理论模型与瞬态响应分析

Theoretical model of walking dynamics and transient response analysis of microtubule-kinesin transport systems

在囊泡运输、遗传物质复制和转录等一系列生命活动中,微管-驱动蛋白输运系统起着至关重要的作用,但其在含黏流体环境中的行走动力学行为仍缺乏相关研究.本文考虑微管的尺度效应和驱动蛋白的步进行走特征,提出了微管-驱动蛋白输运系统的行走动力学新模型,构建了求解该输运系统瞬态响应的理论计算方法,并将动力学模型与准静态模型的结果进行了比较;重点讨论了含黏流体环境中微管-驱动蛋白输运系统在驱动蛋白行走过程中的瞬态动力学响应.研究结果发现,结合状态的切换会使微管产生机械振动,且在切换时刻振幅达到最大,之后慢慢衰减直到稳定.在行走过程中,驱动蛋白颈链内部的轴力呈周期性变化,只与结合状态和指向有关,并且随着步进距离的增加,颈链弯矩和剪力会不断增大.

Kinesin,microtubule and cargo constitute the microtubule-kinesin transport system in cells,which exists in a series of life activities such as vesicle transport,cell division,genetic material replication and transcription.The mechanical regulation error between microtubules and kinesin can lead to the detachment of kinesin and the collapse of microtubules,and even cause cell proliferation failure,canceration or death.There is a lack of relevant research on the walking dynamic behavior of microtubule-kinesin transport system in viscous fluid environment.In this paper,considering the scale effect of microtubule structure and the difference between the longitudinal and transverse interactions of internal dimers,as well as the time-varying topological structure of the transport system during kinesin walking,a new walking dynamics model of microtubule-kinesin transport system is proposed.The theoretical calculation method of the transient response of the transport system is constructed,and the results of the dynamic model and the quasi-static model are compared.We analyze the transient dynamic response of the microtubule-kinesin transport system during kinesin walking in a viscous fluid environment.The results reveal that the transition between the single-head and double-head binding states triggers mechanical vibration in the microtubule.Notably,the amplitude of the displacement curve peaks at the transition point and subsequently decays gradually until stabilization.Furthermore,the microtubule vibration is more intense and exhibits a larger vibration amplitude when kinesin transitions to its double-head binding state.As kinesin progresses,the closer the node position approaches the junction point,the greater the vertical displacement becomes.Additionally,at various time points,the protofilament of the microtubule pathway undergoes local deformation at the site where the protein binds to the microtubule.The unique network structure of the microtubule restricts this deformation to a narrow region proximate to the binding point.The other positions on the microtubule are less affected,and the deflection curve of the microtubuleprotofilament assumes a conical shape.Moreover,at the binding site of the protein and microtubule,the deflection curve peaks,with the number of peaks matching the number of binding points.During the walking process,the axial force within the neck-linker of the kinesin varies periodically,a phenomenon solely linked to the binding state and direction.As the step distance increases,the overall magnitude of bending moment and shear force within the neck-linker continues to rise.In this paper,we propose a walking dynamics model for the microtubule-kinesin transport system,clearly distinguishing the dynamic equations for different binding stages of kinesin and microtubule.In comparison to quasi-static models,our walking dynamics approach enables a more precise and accurate solution of the microtubule-kinesin transport system.This is instrumental in elucidating the mechanical mechanisms underlying the interaction between microtubules and kinesin,deepening our understanding of the motion mechanisms of molecular transport systems,and providing a theoretical foundation for the development of nanomachine walking dynamics.