Force Generated by Two Kinesin Motors Depends on the Load Direction and Intermolecular Coupling

Area of Science:

• Biophysics
• Cell Biology
• Molecular Motors

Background:

• Kinesins are essential molecular motors responsible for intracellular transport of cellular cargoes.
• While single kinesin mechanics are understood, the collective behavior of multiple kinesins exhibits significant experimental variability.
• The underlying reasons for this variability in multi-kinesin systems remain unclear.

Purpose of the Study:

• To investigate the source of variability in the dynamics of multiple kinesin motors.
• To resolve single-motor force measurements into directional components and analyze their impact on motor detachment.
• To explain the observed discrepancies in experimental results concerning kinesin collective behavior.

Main Methods:

• Decomposition of single-motor force measurements into vertical and horizontal components.
• Analysis of how these force components influence kinesin detachment rates.
• Consideration of diverse experimental geometries in the analysis of motor dynamics.

Main Results:

• The vertical force component was found to accelerate kinesin detachment.
• The horizontal force component, opposing motor motion, was observed to decelerate detachment.
• Accounting for force directionality and experimental geometry significantly reduced variability in multi-motor dynamics.

Conclusions:

• The directionality of forces exerted by kinesin motors is a critical factor influencing their detachment dynamics.
• Variability in multi-kinesin experimental outcomes can be largely explained by considering the interplay between force direction and experimental geometry.
• This work provides a unified framework for understanding kinesin collective behavior in diverse cellular contexts.