A fine balance among key biophysical factors is required for recovery of bipolar mitotic spindle from monopolar and multipolar abnormalities

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dc.contributor.authorLi, Xiaochuen
dc.contributor.authorBloomfield, Mathewen
dc.contributor.authorBridgeland, Alexandraen
dc.contributor.authorCimini, Danielaen
dc.contributor.authorChen, Jingen
dc.date.accessioned2024-02-13T13:51:09Zen
dc.date.available2024-02-13T13:51:09Zen
dc.date.issued2023-06-21en
dc.description.abstractDuring mitosis, equal partitioning of chromosomes into two daughter cells requires assembly of a bipolar mitotic spindle. Because the spindle poles are each organized by a centrosome in animal cells, centrosome defects can lead to monopolar or multipolar spindles. However, the cell can effectively recover the bipolar spindle by separating the centrosomes in monopolar spindles and clustering them in multipolar spindles. To interrogate how a cell can separate and cluster centrosomes as needed to form a bipolar spindle, we developed a biophysical model, based on experimental data, which uses effective potential energies to describe key mechanical forces driving centrosome movements during spindle assembly. Our model identified general biophysical factors crucial for robust bipolarization of spindles that start as monopolar or multipolar. These factors include appropriate force fluctuation between centrosomes, balance between repulsive and attractive forces between centrosomes, exclusion of the centrosomes from the cell center, proper cell size and geometry, and a limited centrosome number. Consistently, we found experimentally that bipolar centrosome clustering is promoted as mitotic cell aspect ratio and volume decrease in tetraploid cancer cells. Our model provides mechanistic explanations for many more experimental phenomena and a useful theoretical framework for future studies of spindle assembly.en
dc.description.versionPublished versionen
dc.format.extent16 page(s)en
dc.format.mimetypeapplication/pdfen
dc.identifierARTN ar90 (Article number)en
dc.identifier.doihttps://doi.org/10.1091/mbc.E22-10-0485en
dc.identifier.eissn1939-4586en
dc.identifier.issn1059-1524en
dc.identifier.issue9en
dc.identifier.orcidCimini, Daniela [0000-0002-4082-4894]en
dc.identifier.orcidChen, Jing [0000-0001-6321-0505]en
dc.identifier.pmid37342878en
dc.identifier.urihttps://hdl.handle.net/10919/117969en
dc.identifier.volume34en
dc.language.isoenen
dc.publisherAmerican Society for Cell Biologyen
dc.relation.urihttps://www.ncbi.nlm.nih.gov/pubmed/37342878en
dc.rightsCreative Commons Attribution-NonCommercial-ShareAlike 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/en
dc.subjectCell Biologyen
dc.subjectSmall-Molecule Inhibitoren
dc.subjectCentrosome Separationen
dc.subjectCell-Shapeen
dc.subjectChromosome Motilityen
dc.subjectKinesin-14 Motorsen
dc.subjectCdk2/Cyclin Een
dc.subjectMechanismen
dc.subjectMicrotubulesen
dc.subjectEg5en
dc.subjectOrientationen
dc.subject.meshCentrosomeen
dc.subject.meshAnimalsen
dc.subject.meshCell Cycle Proteinsen
dc.subject.meshCell Cycleen
dc.subject.meshMitosisen
dc.subject.meshSpindle Apparatusen
dc.titleA fine balance among key biophysical factors is required for recovery of bipolar mitotic spindle from monopolar and multipolar abnormalitiesen
dc.title.serialMolecular Biology of The Cellen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.otherArticleen
dc.type.otherJournalen
pubs.organisational-group/Virginia Techen
pubs.organisational-group/Virginia Tech/Scienceen
pubs.organisational-group/Virginia Tech/Science/Biological Sciencesen
pubs.organisational-group/Virginia Tech/Faculty of Health Sciencesen
pubs.organisational-group/Virginia Tech/All T&R Facultyen
pubs.organisational-group/Virginia Tech/Science/COS T&R Facultyen

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