TY - JOUR
T1 - Mechanical Counterbalance of Kinesin and Dynein Motors in a Microtubular Network Regulates Cell Mechanics, 3D Architecture, and Mechanosensing
AU - Zhovmer, Alexander S.
AU - Manning, Alexis
AU - Smith, Chynna
AU - Hayes, James B.
AU - Burnette, Dylan T.
AU - Wang, Jian
AU - Cartagena-Rivera, Alexander X.
AU - Dokholyan, Nikolay V.
AU - Singh, Rakesh K.
AU - Tabdanov, Erdem D.
N1 - Funding Information:
E.D.T. and this work were supported by the Department of Pharmacology, Penn State College of Medicine via the startup funds. A.S.Z. and A.M. were supported by the FDA Intramural Research Program of the Center for Biologics Evaluation and Research. We thank Christian Combs and Daniela Malide for the Light Microscopy Core support at the National Heart, Lung, and Blood Institute, NIH. Work in the Burnette lab was supported by a MIRA to D.T.B. (R35 GM125028), a training grant to J.B.H. (T32 GM08320) and an American Heart Association fellowship to J.B.H. (AHA 836090). A.X.C.R. and C.S. were supported by the National Institutes of Health (NIH) Intramural Research Program in the National Institute of Biomedical Imaging and Bioengineering (NIH grant # ZIA EB000094) and by the NIH Distinguished Scholars Program. N.V.D. is supported by the NIH grant R35GM134864 and the Passan Foundation.
Publisher Copyright:
© 2021 American Chemical Society. All rights reserved.
PY - 2021/11/23
Y1 - 2021/11/23
N2 - 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.
AB - 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.
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U2 - 10.1021/acsnano.1c04435
DO - 10.1021/acsnano.1c04435
M3 - Article
C2 - 34677937
AN - SCOPUS:85118943140
VL - 15
SP - 17528
EP - 17548
JO - ACS Nano
JF - ACS Nano
SN - 1936-0851
IS - 11
ER -