Mechanical Counterbalance of Kinesin and Dynein Motors in a Microtubular Network Regulates Cell Mechanics, 3D Architecture, and Mechanosensing
Open Access
- 22 October 2021
- journal article
- research article
- Published by American Chemical Society (ACS) in ACS Nano
- Vol. 15 (11), 17528-17548
- https://doi.org/10.1021/acsnano.1c04435
Abstract
Microtubules (MTs) and MT motor proteins form active 3D networks made of unstretchable cables with rod-like bending mechanics that provide cells with a dynamically changing structural scaffold. In this study, we report an antagonistic mechanical balance within the dynein–kinesin microtubular motor system. Dynein activity drives the microtubular network inward compaction, while isolated activity of kinesins bundles and expands MTs into giant circular bands that deform the cell cortex into discoids. Furthermore, we show that dyneins recruit MTs to sites of cell adhesion, increasing the topographic contact guidance of cells, while kinesins antagonize it via retraction of MTs from sites of cell adhesion. Actin-to-microtubule translocation of septin-9 enhances kinesin–MT interactions, outbalances the activity of kinesins over that of dyneins, and induces the discoid architecture of cells. These orthogonal mechanisms of MT network reorganization highlight the existence of an intricate mechanical balance between motor activities of kinesins and dyneins that controls cell 3D architecture, mechanics, and cell–microenvironment interactions.Funding Information
- Food and Drug Administration
- American Heart Association (AHA 836090)
- National Institute of Biomedical Imaging and Bioengineering (ZIA EB000094)
- Passano Foundation
- National Institutes of Health
- National Institute of General Medical Sciences (R35 GM125028, R35 GM134864, T32 GM08320)
- Department of Pharmacology, Penn State College of Medicine
This publication has 115 references indexed in Scilit:
- Mechanisms Underlying the Dual-Mode Regulation of Microtubule Dynamics by Kip3/Kinesin-8Molecular Cell, 2011
- Rapid Flexible Docking Using a Stochastic Rotamer Library of LigandsJournal of Chemical Information and Modeling, 2010
- Metastatic breast tumors express increased tau, which promotes microtentacle formation and the reattachment of detached breast tumor cellsOncogene, 2010
- Emerging roles for myosin II and cytoplasmic dynein in migrating neurons and growth conesTrends in Cell Biology, 2009
- The kinesin-14 Klp2 organizes microtubules into parallel bundles by an ATP-dependent sorting mechanismNature, 2009
- MedusaScore: An Accurate Force Field-Based Scoring Function for Virtual Drug ScreeningJournal of Chemical Information and Modeling, 2008
- Myosin II Activity Facilitates Microtubule Bundling in the Neuronal Growth Cone NeckDevelopmental Cell, 2008
- Polarity reveals intrinsic cell chiralityProceedings of the National Academy of Sciences of the United States of America, 2007
- Microtubule function in fibroblast spreading is modulated according to the tension state of cell–matrix interactionsProceedings of the National Academy of Sciences of the United States of America, 2007
- Review: regulation mechanisms of Kinesin-1Journal of Muscle Research and Cell Motility, 2006