Bidirectionality from cargo thermal fluctuations in motor-mediated transport

Area of Science:

• Cellular Biology
• Biophysics
• Molecular Motors

Background:

• Molecular motor proteins are crucial for intracellular transport, generating forces to move cargo along cytoskeletal filaments.
• Bidirectional motion arises when oppositely directed motors (kinesin, dynein) attach to the same cargo.

Purpose of the Study:

• To propose and model cargo diffusion as an alternative mechanism driving directional switching in bidirectionally transported cargoes.
• To investigate the role of thermal fluctuations in motor-cargo dynamics.

Main Methods:

• Developed a mean-field mathematical model incorporating motor-cargo mechanical interactions and cargo thermal fluctuations (diffusion).
• Quantified motor response delay to cargo velocity fluctuations, reducing the model to a characteristic distance proxy for net force.
• Utilized mean first passage time analysis to study switching dynamics.

Main Results:

• The system exhibits metastability, with switching between directional transport states driven solely by cargo diffusion.
• Switching time is non-monotonic with respect to cargo drag, suggesting a testable experimental prediction.

Conclusions:

• Cargo diffusion is a significant factor in the switching dynamics of bidirectionally transported cargoes.
• The model provides a framework for understanding noise-driven transitions in molecular motor systems and offers experimental avenues for validation.