A change point analysis protocol for comparing intracellular transport by different molecular motor combinations

Melanie A. Jensen; Qingzhou Feng; William O. Hancock; Scott A. McKinley; Melanie A. Jensen; Qingzhou Feng; William O. Hancock; Scott A. McKinley

doi:10.3934/mbe.2021442

Mathematical Biosciences and Engineering

2021, Volume 18, Issue 6: 8962-8996. doi: 10.3934/mbe.2021442

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Research article

A change point analysis protocol for comparing intracellular transport by different molecular motor combinations

1.
Department of Mathematics, Tulane University, New Orleans, LA 70118, USA
2.
Department of Biomedical Engineering, Pennsylvania State University, University Park, PA 16802
3.
Molecular Cellular and Integrative Biological Sciences Program, Huck Institute of Life Sciences, Pennsylvania State University, University Park, PA 16802
4.
Schlumberger, 1 Hampshire St Ste 1, Cambridge, MA, 02319 USA
5.
Department of Cell Biology, Yale School of Medicine, Yale University, New Haven, CT 06520

Received: 09 May 2021 Accepted: 06 September 2021 Published: 18 October 2021

Intracellular transport by microtubule-based molecular motors is marked by qualitatively different behaviors. It is a long-standing and still-open challenge to accurately quantify the various individual-cargo behaviors and how they are affected by the presence or absence of particular motor families. In this work we introduce a protocol for analyzing change points in cargo trajectories that can be faithfully projected along the length of a (mostly) straight microtubule. Our protocol consists of automated identification of velocity change points, estimation of velocities during the behavior segments, and extrapolation to motor-specific velocity distributions. Using simulated data we show that our method compares favorably with existing methods. We then apply the technique to data sets in which quantum dots are transported by Kinesin-1, by Dynein-Dynactin-BicD2 (DDB), and by Kinesin-1/DDB pairs. In the end, we identify pausing behavior that is consistent with some tug-of-war model predictions, but also demonstrate that the simultaneous presence of antagonistic motors can lead to long processive runs that could contribute favorably to population-wide transport.
- intracellular transport,
- molecular motors,
- change point analysis
Citation: Melanie A. Jensen, Qingzhou Feng, William O. Hancock, Scott A. McKinley. A change point analysis protocol for comparing intracellular transport by different molecular motor combinations[J]. Mathematical Biosciences and Engineering, 2021, 18(6): 8962-8996. doi: 10.3934/mbe.2021442

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Abstract

Intracellular transport by microtubule-based molecular motors is marked by qualitatively different behaviors. It is a long-standing and still-open challenge to accurately quantify the various individual-cargo behaviors and how they are affected by the presence or absence of particular motor families. In this work we introduce a protocol for analyzing change points in cargo trajectories that can be faithfully projected along the length of a (mostly) straight microtubule. Our protocol consists of automated identification of velocity change points, estimation of velocities during the behavior segments, and extrapolation to motor-specific velocity distributions. Using simulated data we show that our method compares favorably with existing methods. We then apply the technique to data sets in which quantum dots are transported by Kinesin-1, by Dynein-Dynactin-BicD2 (DDB), and by Kinesin-1/DDB pairs. In the end, we identify pausing behavior that is consistent with some tug-of-war model predictions, but also demonstrate that the simultaneous presence of antagonistic motors can lead to long processive runs that could contribute favorably to population-wide transport.

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