Small Crowders Slow Down Kinesin-1 Stepping by Hindering Motor Domain Diffusion

Area of Science:

• Molecular motor function
• Nanomechanics
• Biophysics

Background:

• Kinesin-1 is a dimeric motor protein that moves along microtubules.
• Its force generation mechanism, particularly at low loads, remains under investigation.

Purpose of the Study:

• To investigate the role of diffusion and viscosity in kinesin-1's stepping mechanism.
• To determine how different sized crowders affect kinesin-1's movement under varying viscosities.

Main Methods:

• Utilized varying concentrations of small and large crowders to alter the effective viscosity experienced by kinesin-1.
• Measured kinesin-1's processive movement and force generation under these controlled conditions.

Main Results:

• Small crowders significantly impede kinesin-1's motion at low viscosities (5 mPa·s), indicating diffusion's importance.
• Large crowders had minimal impact on kinesin-1's function even at high viscosities (>100 mPa·s).
• This demonstrates a scale-dependent effect of viscosity on the motor protein's functionality.

Conclusions:

• Diffusion of the tethered motor domain is critical for kinesin-1's stepping mechanism.
• The viscosity scaling paradigm is crucial for understanding nanomechanical systems like kinesin-1.
• Kinesin-1's functionality is highly sensitive to the effective viscosity experienced by its motor domains, especially at low hydrodynamic loads.