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Coarse-grained simulations of actomyosin rings point to a nodeless model involving both unipolar and bipolar myosins

Nguyen, Lam T. and Swulius, Matthew T. and Aich, Samya and Mishra, Mithilesh and Jensen, Grant J. (2018) Coarse-grained simulations of actomyosin rings point to a nodeless model involving both unipolar and bipolar myosins. Molecular Biology of the Cell, 29 (11). pp. 1318-1331. ISSN 1059-1524. PMCID PMC5994903. http://resolver.caltech.edu/CaltechAUTHORS:20180604-082905260

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Abstract

Cytokinesis in many eukaryotic cells is orchestrated by a contractile actomyosin ring. While many of the proteins involved are known, the mechanism of constriction remains unclear. Informed by the existing literature and new three-dimensional (3D) molecular details from electron cryotomography, here we develop 3D coarse-grained models of actin filaments, unipolar and bipolar myosins, actin cross-linkers, and membranes and simulate their interactions. Assuming that local force on the membrane results in inward growth of the cell wall, we explored a matrix of possible actomyosin configurations and found that node-based architectures like those presently described for ring assembly result in membrane puckers not seen in electron microscope images of real cells. Instead, the model that best matches data from fluorescence microscopy, electron cryotomography, and biochemical experiments is one in which actin filaments transmit force to the membrane through evenly distributed, membrane-attached, unipolar myosins, with bipolar myosins in the ring driving contraction. While at this point this model is only favored (not proven), the work highlights the power of coarse-grained biophysical simulations to compare complex mechanistic hypotheses.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1091/mbc.E17-12-0736DOIArticle
https://www.molbiolcell.org/doi/suppl/10.1091/mbc.E17-12-0736PublisherSupplementary Material
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5994903/PubMed CentralArticle
https://doi.org/10.1101/194910DOIDiscussion Paper
ORCID:
AuthorORCID
Jensen, Grant J.0000-0003-1556-4864
Additional Information:© 2018 Nguyen et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). Received: Dec 19, 2017; Revised: Mar 26, 2018; Accepted: Apr 4, 2018; Published Online:31 May 2018. We thank Catherine Oikonomou for helping revise the manuscript for clarity. M.M. is an Intermediate Fellow of the Wellcome Trust−Department of Biotechnology India Alliance (IA/I/14/1/501317). M.M. acknowledges the India Alliance and the Department of Atomic Energy/Tata Institute of Fundamental Research for funds. This work was supported in part by National Institutes of Health Grant GM122588 to G.J.J.
Funders:
Funding AgencyGrant Number
Wellcome Trust−Department of Biotechnology India AllianceIA/I/14/1/501317
Department of Atomic Energy (India)UNSPECIFIED
Tata Institute of Fundamental ResearchUNSPECIFIED
NIHGM122588
PubMed Central ID:PMC5994903
Record Number:CaltechAUTHORS:20180604-082905260
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:20180604-082905260
Official Citation:Coarse-grained simulations of actomyosin rings point to a nodeless model involving both unipolar and bipolar myosins Lam T. Nguyen, Matthew T. Swulius, Samya Aich, Mithilesh Mishra, Grant J. Jensen, and Alex Mogilner Molecular Biology of the Cell 2018 29:11, 1318-1331
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:86773
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:04 Jun 2018 18:24
Last Modified:22 Oct 2018 21:18

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