Title | Microtubule-Based Control of Motor-Clutch System Mechanics in Glioma Cell Migration. |
Publication Type | Journal Article |
Year of Publication | 2018 |
Authors | Prahl LS, Bangasser PF, Stopfer LE, Hemmat M, White FM, Rosenfeld SS, Odde DJ |
Journal | Cell Rep |
Volume | 25 |
Issue | 9 |
Pagination | 2591-2604.e8 |
Date Published | 2018 Nov 27 |
ISSN | 2211-1247 |
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. |
DOI | 10.1016/j.celrep.2018.10.101 |
Alternate Journal | Cell Rep |
PubMed ID | 30485822 |
PubMed Central ID | PMC6345402 |
Grant List | R01 NS073610 / NS / NINDS NIH HHS / United States R01 GM076177 / GM / NIGMS NIH HHS / United States T32 ES007020 / ES / NIEHS NIH HHS / United States U54 CA210190 / CA / NCI NIH HHS / United States R01 CA172986 / CA / NCI NIH HHS / United States U54 CA210180 / CA / NCI NIH HHS / United States |