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Published June 1, 2018 | Submitted + Published + Supplemental Material
Journal Article Open

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

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.

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.

Attached Files

Published - mbc.e17-12-0736.pdf

Submitted - 194910.full.pdf

Supplemental Material - combinedsupmats.pdf

Supplemental Material - e17-12-0736_zipfile.gz

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Created:
August 19, 2023
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October 20, 2023