{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T10:24:01Z","timestamp":1767176641537,"version":"build-2238731810"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1010165","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,6,15]],"date-time":"2022-06-15T00:00:00Z","timestamp":1655251200000}}],"reference-count":91,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2022,6,3]],"date-time":"2022-06-03T00:00:00Z","timestamp":1654214400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01HL148227"],"award-info":[{"award-number":["R01HL148227"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["MCB-2027530"],"award-info":[{"award-number":["MCB-2027530"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["DMS1953430"],"award-info":[{"award-number":["DMS1953430"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>We introduce a Stochastic Reaction-Diffusion-Dynamics Model (SRDDM) for simulations of cellular mechanochemical processes with high spatial and temporal resolution. The SRDDM is mapped into the CellDynaMo package, which couples the spatially inhomogeneous reaction-diffusion master equation to account for biochemical reactions and molecular transport within the Langevin Dynamics (LD) framework to describe dynamic mechanical processes. This computational infrastructure allows the simulation of hours of molecular machine dynamics in reasonable wall-clock time. We apply SRDDM to test performance of the Search-and-Capture of mitotic spindle assembly by simulating, in three spatial dimensions, dynamic instability of elastic microtubules anchored in two centrosomes, movement and deformations of geometrically realistic centromeres with flexible kinetochores and chromosome arms. Furthermore, the SRDDM describes the mechanics and kinetics of Ndc80 linkers mediating transient attachments of microtubules to the chromosomal kinetochores. The rates of these attachments and detachments depend upon phosphorylation states of the Ndc80 linkers, which are regulated in the model by explicitly accounting for the reactions of Aurora A and B kinase enzymes undergoing restricted diffusion. We find that there is an optimal rate of microtubule-kinetochore detachments which maximizes the accuracy of the chromosome connections, that adding chromosome arms to kinetochores improve the accuracy by slowing down chromosome movements, that Aurora A and kinetochore deformations have a small positive effect on the attachment accuracy, and that thermal fluctuations of the microtubules increase the rates of kinetochore capture and also improve the accuracy of spindle assembly.<\/jats:p>","DOI":"10.1371\/journal.pcbi.1010165","type":"journal-article","created":{"date-parts":[[2022,6,3]],"date-time":"2022-06-03T13:58:11Z","timestamp":1654264691000},"page":"e1010165","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":11,"title":["CellDynaMo\u2013stochastic reaction-diffusion-dynamics model: Application to search-and-capture process of mitotic spindle assembly"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2410-2138","authenticated-orcid":true,"given":"Evgenii","family":"Kliuchnikov","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4414-8352","authenticated-orcid":true,"given":"Artem","family":"Zhmurov","sequence":"additional","affiliation":[]},{"given":"Kenneth A.","family":"Marx","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5302-2404","authenticated-orcid":true,"given":"Alex","family":"Mogilner","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1994-3917","authenticated-orcid":true,"given":"Valeri","family":"Barsegov","sequence":"additional","affiliation":[]}],"member":"340","published-online":{"date-parts":[[2022,6,3]]},"reference":[{"key":"pcbi.1010165.ref001","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.ceb.2009.01.002","article-title":"Cell fate regulation by coupling mechanical cycles to biochemical signaling pathways","volume":"21","author":"V Vogel","year":"2009","journal-title":"Curr Opin Cell Biol"},{"key":"pcbi.1010165.ref002","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/nature01599","article-title":"Cell division","volume":"422","author":"JM Scholey","year":"2003","journal-title":"Nature"},{"key":"pcbi.1010165.ref003","first-page":"5","article-title":"A molecular view of kinetochore assembly and function","volume":"6","author":"A Musacchio","year":"2017","journal-title":"Biology (Basel)"},{"key":"pcbi.1010165.ref004","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1016\/j.tcb.2005.09.010","article-title":"Kinetochore structure and function","volume":"15","author":"GK Chan","year":"2005","journal-title":"Trends Cell Biol"},{"key":"pcbi.1010165.ref005","doi-asserted-by":"crossref","first-page":"e36764","DOI":"10.7554\/eLife.36764","article-title":"Multivalency of NDC80 in the outer kinetochore is essential to track shortening microtubules and generate forces","volume":"7","author":"VA Volkov","year":"2018","journal-title":"Elife"},{"key":"pcbi.1010165.ref006","doi-asserted-by":"crossref","first-page":"1134","DOI":"10.1038\/ncb3223","article-title":"Adaptive changes in the kinetochore architecture facilitate proper spindle assembly","volume":"17","author":"V Magidson","year":"2015","journal-title":"Nat Cell Biol"},{"key":"pcbi.1010165.ref007","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1146\/annurev-biophys-042910-155227","article-title":"Decision making in living cells: Lessons from a simple system","volume":"40","author":"I. 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