Collective Dynamics of Kinesin-1.

Motor Proteins;Coupled Oscillators;Synchronization;Kinesin;Mechanical Engineering;Engineering;Mechanical Engineering

Hendricks, Adam G.Hunt, Alan J. ;

University of Michigan

关键词: Motor Proteins;    Coupled Oscillators;    Synchronization;    Kinesin;    Mechanical Engineering;    Engineering;    Mechanical Engineering;   

Others  :  https://deepblue.lib.umich.edu/bitstream/handle/2027.42/60661/adhendri_1.pdf?sequence=1&isAllowed=y

瑞士|英语

来源: The Illinois Digital Environment for Access to Learning and Scholarship

【 摘 要 】

Motor proteins are the engines of biology, converting chemical energy to mechanical work in cells. Kinesin-1 is a motor protein that transports vesicles towards the plus end of microtubules, widely believed to be responsible for anterograde transport of synaptic vesicles in neurons. Advances in single-molecule techniques have allowed the characterization of single kinesin motors in vitro at a range of loads and ATP concentrations. Single kinesin motors are capable of processive movement along themicrotubule at a maximum velocity of approximately 1 μm/s. The velocity decreases roughly linearly in response to load until reaching stall at a load of approximately6 pN. Several theoretical models have been proposed that describe the steady-state motion of single kinesin motors. However, growing evidence suggests that kinesin functions collectively in cells, whereby several motors work in a coordinated manner to transport a vesicle. A transient description is required to describe collective dynamics, as the interactions among coupled motors induce time-varying forces on each motor. Herein a mechanistic model of kinesin is proposed that is capable of accurately describing transient and steady-state dynamics. Each domain of the protein is modeled via a mechanical potential. The mechanical potentials are relatedexplicitly to the chemical kinetics of each motor domain. The mechanistic model was used to simulate the collective behavior of coupled kinesin motors under varying loads, cargo linker stiffnesses, and numbers of motors. To analyze the simulations of coordinated transport, several metrics were developed that are specifically tailored to characterizing the synchronization of nonlinear, nonsmooth oscillators like kinesin. The model results suggest that, in the cell, coupled motors under low loads are loosely correlated. When the load is increased, such as when the cargo encounters an obstacle like another vesicle or the cytoskeleton, motors become more correlated in response to increased loads, allowing them to produce greater forces. Increasing the number of motors involved in the transport does not appreciably increase the dimensionality of the trajectory, implying large numbers of motors are able to work collectively, even without becoming fully synchronized.