Microtubule-Based Control of Motor-Clutch System Mechanics in Glioma Cell Migration
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Author(s)
Prahl, Louis S.
Bangasser, Patrick F.
Stopfer, Lauren Elizabeth
Hemmat, Mahya
White, Forest M.
Rosenfeld, Steven S.
Odde, David J.
Date Issued
November 2018
Journal
Cell Reports
Publisher
Cell Press
Citation
Prahl, Louis S., Patrick F. Bangasser, Lauren E. Stopfer, Mahya Hemmat, Forest M. White, Steven S. Rosenfeld, and David J. Odde. “Microtubule-Based Control of Motor-Clutch System Mechanics in Glioma Cell Migration.” Cell Reports 25, 9 (November 2018): p. 2591–2604.e8. doi. 10.1016/j.celrep.2018.10.101 ©2018 Authors
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Final published version
Abstract
Microtubule-targeting agents (MTAs) are widely used chemotherapy drugs capable of disrupting microtubule-dependent cellular functions, such as division and migration. We show that two clinically approved MTAs, paclitaxel and vinblastine, each suppress stiffness-sensitive migration and polarization characteristic of human glioma cells on compliant hydrogels. MTAs influence microtubule dynamics and cell traction forces by nearly opposite mechanisms, the latter of which can be explained by a combination of changes in myosin motor and adhesion clutch number. Our results support a microtubule-dependent signaling-based model for controlling traction forces through a motor-clutch mechanism, rather than microtubules directly relieving tension within F-actin and adhesions. Computational simulations of cell migration suggest that increasing protrusion number also impairs stiffness-sensitive migration, consistent with experimental MTA effects. These results provide a theoretical basis for the role of microtubules and mechanisms of MTAs in controlling cell migration. Prahl et al. examine the mechanisms by which microtubule-targeting drugs inhibit glioma cell migration. They find that dynamic microtubules regulate actin-based protrusion dynamics that facilitate cell polarity and migration. Changes in net microtubule assembly alter cell traction forces via signaling-based regulation of a motor-clutch system. ©2018 The Authors
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Koch Institute for Integrative Cancer Research at MIT
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Creative Commons Attribution 4.0 International license
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DOI of Published Version
https://doi.org/10.1016/j.celrep.2018.10.101
