Tunable intracellular transport on converging microtubule morphologies

Area of Science:

• Cell Biology
• Biophysics
• Systems Biology

Background:

• Cellular transport relies on motor proteins moving along cytoskeletal tracks like microtubules.
• Microtubule organizing centers (MTOCs) are crucial for organizing microtubules and directing intracellular transport.
• The precise mechanisms governing cargo dynamics and efficiency near MTOCs remain incompletely understood.

Purpose of the Study:

• To investigate the principles governing the dynamics, efficiency, and tunability of cargo transport in the vicinity of the MTOC.
• To model the interplay between directed (advective) and random (diffusive) transport processes.
• To quantify how cargo attachment and detachment rates influence transport outcomes.

Main Methods:

• Development of a one-dimensional model incorporating advective transport towards an attractor (MTOC) and diffusive transport to absorbing boundaries.
• Calculation of the mean first passage time (MFPT) to assess cargo sequestering and dispersal effectiveness.
• Analysis of the impact of varying cargo on-/off-rates and MTOC positioning on transport dynamics.

Main Results:

• A transition from dispersal to sequestering (low to high MFPT) occurs within a physiological range of cargo on-/off-rates.
• Optimal cargo dispersal can be achieved by tuning attachment/detachment rates, especially with asymmetric MTOC placement.
• A rare event regime reveals exponential scaling of MFPT with motor velocity and sensitivity to MTOC position.

Conclusions:

• MTOCs act as critical regulators of intracellular transport, enabling precise spatial and temporal control of cargo.
• The model provides insights into how cells manage cargo distribution and function through tunable transport mechanisms.
• Findings highlight the importance of motor protein dynamics and MTOC architecture in cellular organization.