Sculpting Rupture-Free Nuclear Shapes in Fibrous Environments
| dc.contributor.author | Aniket, Jana | en |
| dc.contributor.author | Tran, Avery | en |
| dc.contributor.author | Gill, Amritpal | en |
| dc.contributor.author | Kiepas, Alexander | en |
| dc.contributor.author | Kapania, Rakesh K. | en |
| dc.contributor.author | Konstantopoulos, Konstantinos | en |
| dc.contributor.author | Nain, Amrinder S. | en |
| dc.date.accessioned | 2023-04-06T18:34:17Z | en |
| dc.date.available | 2023-04-06T18:34:17Z | en |
| dc.date.issued | 2022 | en |
| dc.description.abstract | Cytoskeleton-mediated force transmission regulates nucleus morphology. How nuclei shaping occurs in fibrous in vivo environments remains poorly understood. Here suspended nanofiber networks of precisely tunable (nm–μm) diameters are used to quantify nucleus plasticity in fibrous environments mimicking the natural extracellular matrix. Contrary to the apical cap over the nucleus in cells on 2-dimensional surfaces, the cytoskeleton of cells on fibers displays a uniform actin network caging the nucleus. The role of contractility-driven caging in sculpting nuclear shapes is investigated as cells spread on aligned single fibers, doublets, and multiple fibers of varying diameters. Cell contractility increases with fiber diameter due to increased focal adhesion clustering and density of actin stress fibers, which correlates with increased mechanosensitive transcription factor Yes-associated protein (YAP) translocation to the nucleus. Unexpectedly, large- and small-diameter fiber combinations lead to teardrop-shaped nuclei due to stress fiber anisotropy across the cell. As cells spread on fibers, diameter-dependent nuclear envelope invaginations that run the nucleus’s length are formed at fiber contact sites. The sharpest invaginations enriched with heterochromatin clustering and sites of DNA repair are insufficient to trigger nucleus rupture. Overall, the authors quantitate the previously unknown sculpting and adaptability of nuclei to fibrous environments with pathophysiological implications. | en |
| dc.description.sponsorship | The authors thank the Institute of Critical Technologies and Sciences (ICTAS) and Macromolecules Innovation Institute at Virginia Tech for the support to conduct this study. A.S.N. acknowledges partial support for this study from National Science Foundation (NSF grant # 1762634 and 2107332) and K.K. acknowledges support from National Institutes of Health (NIH grants R01 GM142175 and RO1 CA254193). | en |
| dc.description.version | Published version | en |
| dc.format.mimetype | application/pdf | en |
| dc.identifier.doi | https://doi.org/10.1101/2021.10.19.465049 | en |
| dc.identifier.issue | 9 | en |
| dc.identifier.uri | http://hdl.handle.net/10919/114358 | en |
| dc.identifier.volume | 2022 | en |
| dc.language.iso | en | en |
| dc.publisher | Wiley | en |
| dc.rights | Creative Commons Attribution 4.0 International | en |
| dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | en |
| dc.title | Sculpting Rupture-Free Nuclear Shapes in Fibrous Environments | en |
| dc.title.serial | Advanced Science | en |
| dc.type | Article - Refereed | en |
| dc.type.dcmitype | Text | en |