Motor protein transport along inhomogeneous microtubules

DOI10.1007/S11538-020-00838-4MaRDI QIDQ2659787zbMATH OpenOpenAlexWikidataFDO

Authors Shawn D. Ryan, Zachary McCarthy, Mykhailo Potomkin

Publication date 26 March 2021

Published in Bulletin of Mathematical Biology (Search for Journal in Brave)

Full work available at URL https://arxiv.org/abs/2005.01955

zbMATH Keywords

defective transportmathematical biologymicrotubulesmotor proteinsphase transitions

Mathematics Subject Classification ID

Qualitative investigation and simulation of ordinary differential equation models (34C60) Applications of difference equations (39A60) Neural biology (92C20) Pathology, pathophysiology (92C32) Cell biology (92C37)

Abstract: Many cellular processes rely on the cell's ability to transport material to and from the nucleus. Networks consisting of many microtubules and actin filaments are key to this transport. Recently, the inhibition of intracellular transport has been implicated in neurodegenerative diseases such as Alzheimer's disease and Amyotrophic Lateral Sclerosis (ALS). Furthermore, microtubules may contain so-called defective regions where motor protein velocity is reduced due to accumulation of other motors and microtubule associated proteins. In this work, we propose a new mathematical model describing the motion of motor proteins on microtubules which incorporate a defective region. We take a mean-field approach derived from a first principle lattice model to study motor protein dynamics and density profiles. In particular, given a set of model parameters we obtain a closed-form expression for the equilibrium density profile along a given microtubule. We then verify the analytic results using mathematical analysis on the discrete model and Monte Carlo simulations. This work will contribute to the fundamental understanding of inhomogeneous microtubules providing insight into microscopic interactions that may result in the onset of neurodegenerative diseases. Our results for inhomogeneous microtubules are consistent with prior work studying the homogeneous case.

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Cites work

• Introduction to perturbation methods
• Spatial pattern formation in microtubule post-translational modifications and the tight localization of motor-driven cargo
• Stochastic modeling reveals how motor protein and filament properties affect intermediate filament transport
• Transport by molecular motors in the presence of static defects

Cited in

(7)

• Traffic of molecular motors through tube-like compartments
• Cargo distributions differentiate pathological axonal transport impairments
• Mathematical modeling of the intracellular protein dynamics: the importance of active transport along microtubules
• Isogeometric analysis-based physics-informed graph neural network for studying traffic jam in neurons
• A hopping mechanism for cargo transport by molecular motors on crowded microtubules
• From the cell membrane to the nucleus: unearthing transport mechanisms for dynein
• Microtubule patterning in the presence of moving motor proteins

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