Mitotic outcomes and errors in fibrous environments
| dc.contributor.author | Jana, Aniket | en |
| dc.contributor.author | Sarkar, Apurba | en |
| dc.contributor.author | Zhang, Haonan | en |
| dc.contributor.author | Agashe, Atharva | en |
| dc.contributor.author | Wang, Ji | en |
| dc.contributor.author | Paul, Raja | en |
| dc.contributor.author | Gov, Nir S. | en |
| dc.contributor.author | DeLuca, Jennifer G. | en |
| dc.contributor.author | Nain, Amrinder S. | en |
| dc.date.accessioned | 2023-04-06T18:33:53Z | en |
| dc.date.available | 2023-04-06T18:33:53Z | en |
| dc.date.issued | 2023-02-27 | en |
| dc.description.abstract | During mitosis, cells round up and utilize the interphase adhesion sites within the fibrous extracellular matrix (ECM) as guidance cues to orient the mitotic spindles. Here, using suspended ECM-mimicking nanofiber networks, we explore mitotic outcomes and error distribution for various interphase cell shapes. Elongated cells attached to single fibers through two focal adhesion clusters (FACs) at their extremities result in perfect spherical mitotic cell bodies that undergo significant 3-dimensional (3D) displacement while being held by retraction fibers (RFs). Increasing the number of parallel fibers increases FACs and retraction fiber-driven stability, leading to reduced 3D cell body movement, metaphase plate rotations, increased interkinetochore distances, and significantly faster division times. Interestingly, interphase kite shapes on a crosshatch pattern of four fibers undergo mitosis resembling single-fiber outcomes due to rounded bodies being primarily held in position by RFs from two perpendicular suspended fibers. We develop a cortex–astral microtubule analytical model to capture the retraction fiber dependence of the metaphase plate rotations. We observe that reduced orientational stability, on single fibers, results in increased monopolar mitotic defects, while multipolar defects become dominant as the number of adhered fibers increases. We use a stochastic Monte Carlo simulation of centrosome, chromosome, and membrane interactions to explain the relationship between the observed propensity of monopolar and multipolar defects and the geometry of RFs. Overall, we establish that while bipolar mitosis is robust in fibrous environments, the nature of division errors in fibrous microenvironments is governed by interphase cell shapes and adhesion geometries. | en |
| dc.description.sponsorship | A.S.N. acknowledges partial funding support from the NSF (grant nos. 1762468 and 2119949). A.S.N. acknowledges the Institute of Critical Technologies and Science (ICTAS) and Macromolecules Innovative Institute (MII) at the Virginia Tech for their support in conducting this study. N.S.G. is the incumbent of Lee and William Abramowitz Professorial Chair of Biophysics, and this research was supported by the Israel Science Foundation (grant no. 1459/17). J.G.D. acknowledges funding support from the NIH (R35GM130365). A.S. and R.P. acknowledge funding support from the IACS, Kolkata. | en |
| dc.description.version | Published version | en |
| dc.format.mimetype | application/pdf | en |
| dc.identifier.doi | https://doi.org/10.1073/pnas.2120536120 | en |
| dc.identifier.issue | 10 | en |
| dc.identifier.uri | http://hdl.handle.net/10919/114357 | en |
| dc.identifier.volume | 120 | en |
| dc.language.iso | en | en |
| dc.publisher | National Academy of Sciences | en |
| dc.rights | Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International | en |
| dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | en |
| dc.subject | mitotic cell rounding | en |
| dc.subject | cell division | en |
| dc.subject | nanofibers | en |
| dc.subject | mitotic spindle | en |
| dc.subject | retraction fibers | en |
| dc.title | Mitotic outcomes and errors in fibrous environments | en |
| dc.title.serial | PNAS | en |
| dc.type | Article - Refereed | en |
| dc.type.dcmitype | Text | en |