{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T15:51:28Z","timestamp":1790697088533,"version":"4.1.0"},"reference-count":48,"publisher":"AIP Publishing","issue":"1","license":[{"start":{"date-parts":[[2022,1,4]],"date-time":"2022-01-04T00:00:00Z","timestamp":1641254400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2022,1,4]],"date-time":"2022-01-04T00:00:00Z","timestamp":1641254400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U01 CA225566"],"award-info":[{"award-number":["U01 CA225566"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004917","name":"Cancer Prevention and Research Institute of Texas","doi-asserted-by":"publisher","award":["RR200043"],"award-info":[{"award-number":["RR200043"]}],"id":[{"id":"10.13039\/100004917","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["pubs.aip.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,3,1]]},"abstract":"<jats:p>The cell nucleus is commonly considered to be a stiff organelle that mechanically resists changes in shape, and this resistance is thought to limit the ability of cells to migrate through pores or spread on surfaces. Generation of stresses on the cell nucleus during migration and nuclear response to these stresses is fundamental to cell migration and mechano-transduction. In this Perspective, we discuss our previous experimental and computational evidence that supports a dynamic model, in which the soft nucleus is irreversibly shaped by viscous stresses generated by the motion of cell boundaries and transmitted through the intervening cytoskeletal network. While the nucleus is commonly modeled as a stiff elastic body, we review how nuclear shape changes on the timescale of migration can be explained by simple geometric constraints of constant nuclear volume and constant surface area of the nuclear lamina. Because the lamina surface area is in excess of that of a sphere of the same volume, these constraints permit dynamic transitions between a wide range of shapes during spreading and migration. The excess surface area allows the nuclear shape changes to mirror those of the cell with little mechanical resistance. Thus, the nucleus can be easily shaped by the moving cell boundaries over a wide range of shape changes and only becomes stiff to more extreme deformations that would require the lamina to stretch or the volume to compress. This model explains how nuclei can easily flatten on surfaces during cell spreading or elongate as cells move through pores until the lamina smooths out and becomes tense.<\/jats:p>","DOI":"10.1063\/5.0071652","type":"journal-article","created":{"date-parts":[[2022,1,4]],"date-time":"2022-01-04T13:22:15Z","timestamp":1641302535000},"update-policy":"https:\/\/doi.org\/10.1063\/aip-crossmark-policy-page","source":"Crossref","is-referenced-by-count":28,"title":["Viscous shaping of the compliant cell nucleus"],"prefix":"10.1063","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7415-2889","authenticated-orcid":false,"given":"Richard B.","family":"Dickinson","sequence":"first","affiliation":[{"name":"Department of Chemical Engineering, University of Florida 1 , Gainesville, Florida 32611, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2888-6320","authenticated-orcid":false,"given":"Aditya","family":"Katiyar","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Texas A&M University 2 , College Station, Texas 77843, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2628-5342","authenticated-orcid":false,"given":"Christina R.","family":"Dubell","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Texas A&M University 2 , College Station, Texas 77843, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8574-1251","authenticated-orcid":false,"given":"Tanmay P.","family":"Lele","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Texas A&M University 2 , College Station, Texas 77843, USA"},{"name":"Artie McFerrin Department of Chemical Engineering, Texas A&M University 3 , College Station, Texas 77843, USA"},{"name":"Department of Translational Medical Sciences, Texas A&M University 4 , Houston, Texas 77843, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"317","published-online":{"date-parts":[[2022,1,4]]},"reference":[{"key":"2024070320505977700_c1","doi-asserted-by":"publisher","first-page":"1069","DOI":"10.1083\/jcb.201210152","article-title":"Physical limits of cell migration: Control by ECM space and nuclear deformation and tuning by proteolysis and traction force","volume":"201","year":"2013","journal-title":"J. Cell Biol."},{"key":"2024070320505977700_c2","doi-asserted-by":"publisher","first-page":"1446","DOI":"10.1002\/jcp.26031","article-title":"The nucleus is irreversibly shaped by motion of cell boundaries in cancer and non-cancer cells","volume":"233","year":"2018","journal-title":"J. Cell. Physiol."},{"key":"2024070320505977700_c3","doi-asserted-by":"publisher","first-page":"7362","DOI":"10.1038\/srep07362","article-title":"Super-resolution microscopy reveals LINC complex recruitment at nuclear indentation sites","volume":"4","year":"2014","journal-title":"Sci. Rep."},{"key":"2024070320505977700_c4","doi-asserted-by":"publisher","first-page":"19017","DOI":"10.1073\/pnas.0908686106","article-title":"A perinuclear actin cap regulates nuclear shape","volume":"106","year":"2009","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"2024070320505977700_c5","doi-asserted-by":"publisher","first-page":"e107895","DOI":"10.1371\/journal.pone.0107895","article-title":"Role of actin filaments in correlating nuclear shape and cell spreading","volume":"9","year":"2014","journal-title":"PLoS One"},{"key":"2024070320505977700_c6","doi-asserted-by":"publisher","first-page":"13200","DOI":"10.1073\/pnas.1902035116","article-title":"Regulation of nuclear architecture, mechanics, and nucleocytoplasmic shuttling of epigenetic factors by cell geometric constraints","volume":"116","year":"2019","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"2024070320505977700_c7","doi-asserted-by":"publisher","first-page":"670","DOI":"10.1016\/j.bpj.2015.07.006","article-title":"Moving cell boundaries drive nuclear shaping during cell spreading","volume":"109","year":"2015","journal-title":"Biophys. J."},{"key":"2024070320505977700_c8","doi-asserted-by":"publisher","first-page":"19689","DOI":"10.1038\/srep19689","article-title":"Vertical uniformity of cells and nuclei in epithelial monolayers","volume":"6","year":"2016","journal-title":"Sci. Rep."},{"key":"2024070320505977700_c9","doi-asserted-by":"publisher","first-page":"1124","DOI":"10.1126\/science.7684161","article-title":"Mechanotransduction across the cell surface and through the cytoskeleton","volume":"260","year":"1993","journal-title":"Science"},{"key":"2024070320505977700_c10","doi-asserted-by":"publisher","first-page":"1215","DOI":"10.1242\/jcs.103.4.1215","article-title":"Altering the cellular mechanical force balance results in integrated changes in cell, cytoskeletal and nuclear shape","volume":"103","year":"1992","journal-title":"J. Cell Sci."},{"key":"2024070320505977700_c11","doi-asserted-by":"publisher","first-page":"1984","DOI":"10.1091\/mbc.e16-09-0653","article-title":"Chromatin and lamin A determine two different mechanical response regimes of the cell nucleus","volume":"28","year":"2017","journal-title":"Mol. Biol. Cell"},{"key":"2024070320505977700_c12","doi-asserted-by":"publisher","first-page":"15619","DOI":"10.1073\/pnas.0702576104","article-title":"Physical plasticity of the nucleus in stem cell differentiation","volume":"104","year":"2007","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"2024070320505977700_c13","doi-asserted-by":"publisher","first-page":"2855","DOI":"10.1529\/biophysj.105.062554","article-title":"Power-law rheology of isolated nuclei with deformation mapping of nuclear substructures","volume":"89","year":"2005","journal-title":"Biophys. J."},{"key":"2024070320505977700_c14","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1038\/ncomms1668","article-title":"Spatial coordination between cell and nuclear shape within micropatterned endothelial cells","volume":"3","year":"2012","journal-title":"Nat. Commun."},{"key":"2024070320505977700_c15","doi-asserted-by":"publisher","first-page":"961","DOI":"10.1016\/j.biomaterials.2013.10.037","article-title":"The regulation of dynamic mechanical coupling between actin cytoskeleton and nucleus by matrix geometry","volume":"35","year":"2014","journal-title":"Biomaterials"},{"key":"2024070320505977700_c16","doi-asserted-by":"publisher","first-page":"4779","DOI":"10.1242\/jcs.01357","article-title":"The nuclear envelope lamina network has elasticity and a compressibility limit suggestive of a molecular shock absorber","volume":"117","year":"2004","journal-title":"J. Cell Sci."},{"key":"2024070320505977700_c17","doi-asserted-by":"publisher","first-page":"1240104","DOI":"10.1126\/science.1240104","article-title":"Nuclear lamin-A scales with tissue stiffness and enhances matrix-directed differentiation","volume":"341","year":"2013","journal-title":"Science"},{"key":"2024070320505977700_c18","doi-asserted-by":"publisher","first-page":"120662","DOI":"10.1016\/j.biomaterials.2021.120662","article-title":"Nuclear envelope wrinkling predicts mesenchymal progenitor cell mechano-response in 2D and 3D microenvironments","volume":"270","year":"2021","journal-title":"Biomaterials"},{"key":"2024070320505977700_c19","doi-asserted-by":"publisher","first-page":"1654","DOI":"10.1016\/j.bpj.2017.08.034","article-title":"Mechanics and Buckling of Biopolymeric Shells and Cell Nuclei","volume":"113","year":"2017","journal-title":"Biophys. J."},{"key":"2024070320505977700_c20","doi-asserted-by":"publisher","first-page":"1901","DOI":"10.1242\/jcs.161703","article-title":"The nucleus is an intracellular propagator of tensile forces in NIH 3T3 fibroblasts","volume":"128","year":"2015","journal-title":"J. Cell Sci."},{"key":"2024070320505977700_c21","doi-asserted-by":"publisher","first-page":"9310","DOI":"10.1039\/C9SM01666J","article-title":"Nuclear size changes caused by local motion of cell boundaries unfold the nuclear lamina and dilate chromatin and intranuclear bodies","volume":"15","year":"2019","journal-title":"Soft Matter"},{"key":"2024070320505977700_c22","doi-asserted-by":"publisher","first-page":"20675","DOI":"10.1002\/jcp.28672","article-title":"Apical cell protrusions cause vertical deformation of the soft cancer nucleus","volume":"234","year":"2019","journal-title":"J. Cell Physiol."},{"key":"2024070320505977700_c23","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1126\/science.aad7297","article-title":"Nuclear envelope rupture and repair during cancer cell migration","volume":"352","year":"2016","journal-title":"Science"},{"key":"2024070320505977700_c24","doi-asserted-by":"publisher","first-page":"1534","DOI":"10.1039\/C5IB00200A","article-title":"Design of a microfluidic device to quantify dynamic intra-nuclear deformation during cell migration through confining environments","volume":"7","year":"2015","journal-title":"Integr. Biol."},{"key":"2024070320505977700_c25","doi-asserted-by":"publisher","first-page":"E8618","DOI":"10.1073\/pnas.1705179114","article-title":"Cell volume change through water efflux impacts cell stiffness and stem cell fate","volume":"114","year":"2017","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"2024070320505977700_c26","doi-asserted-by":"publisher","first-page":"460","DOI":"10.1002\/jcb.22437","article-title":"The effects of osmotic stress on the structure and function of the cell nucleus","volume":"109","year":"2010","journal-title":"J. Cell Biochem."},{"key":"2024070320505977700_c27","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1083\/jcb.200708054","article-title":"Nuclear size control in fission yeast","volume":"179","year":"2007","journal-title":"J. Cell Biol."},{"key":"2024070320505977700_c28","doi-asserted-by":"publisher","first-page":"3523","DOI":"10.1091\/mbc.e06-10-0973","article-title":"The size of the nucleus increases as yeast cells grow","volume":"18","year":"2007","journal-title":"Mol. Biol. Cell"},{"key":"2024070320505977700_c29","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1016\/j.cell.2010.09.012","article-title":"Nuclear size is regulated by importin alpha and Ntf2 in Xenopus","volume":"143","year":"2010","journal-title":"Cell"},{"key":"2024070320505977700_c30","doi-asserted-by":"publisher","first-page":"4984","DOI":"10.1529\/biophysj.107.116863","article-title":"Micropatterning of single endothelial cell shape reveals a tight coupling between nuclear volume in G1 and proliferation","volume":"94","year":"2008","journal-title":"Biophys. J."},{"key":"2024070320505977700_c31","doi-asserted-by":"publisher","first-page":"e8560","DOI":"10.1371\/journal.pone.0008560","article-title":"Myosin II motor proteins with different functions determine the fate of lamellipodia extension during cell spreading","volume":"5","year":"2010","journal-title":"PLoS One"},{"key":"2024070320505977700_c32","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1083\/jcb.200806030","article-title":"Segregation and activation of myosin IIB creates a rear in migrating cells","volume":"183","year":"2008","journal-title":"J. Cell Biol."},{"key":"2024070320505977700_c33","doi-asserted-by":"publisher","first-page":"5714","DOI":"10.1002\/jcp.30256","article-title":"Osteoprotegerin is sensitive to actomyosin tension in human periodontal ligament fibroblasts","volume":"236","year":"2021","journal-title":"J. Cell. Physiol."},{"key":"2024070320505977700_c34","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1016\/S0025-5564(98)10067-6","article-title":"Cytoplasm dynamics and cell motion: Two-phase flow models","volume":"156","year":"1999","journal-title":"Math. Biosci."},{"key":"2024070320505977700_c35","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1038\/nmat3517","article-title":"The cytoplasm of living cells behaves as a poroelastic material","volume":"12","year":"2013","journal-title":"Nat. Mater."},{"key":"2024070320505977700_c36","doi-asserted-by":"publisher","first-page":"1265","DOI":"10.1016\/j.bpj.2012.08.028","article-title":"Self-organization of myosin II in reconstituted actomyosin bundles","volume":"103","year":"2012","journal-title":"Biophys. J."},{"key":"2024070320505977700_c37","doi-asserted-by":"publisher","first-page":"e0131920","DOI":"10.1371\/journal.pone.0131920","article-title":"Non-muscle myosin II isoforms have different functions in matrix rearrangement by MDA-MB-231 cells","volume":"10","year":"2015","journal-title":"PLoS One"},{"key":"2024070320505977700_c38","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1146\/annurev-fluid-010816-060238","article-title":"Intracellular fluid mechanics: Coupling cytoplasmic flow with active cytoskeletal gel","volume":"50","year":"2018","journal-title":"Annu. Rev. Fluid Mech."},{"key":"2024070320505977700_c39","doi-asserted-by":"publisher","first-page":"10134","DOI":"10.1038\/ncomms10134","article-title":"Local viscoelasticity of living cells measured by rotational magnetic spectroscopy","volume":"7","year":"2016","journal-title":"Nat. Commun."},{"key":"2024070320505977700_c40","volume-title":"Cytoskeletal Mechanics: Models and Measurements in Cell Mechanics","year":"2006"},{"key":"2024070320505977700_c41","doi-asserted-by":"publisher","first-page":"5561","DOI":"10.3390\/s21165561","article-title":"A cell's viscoelasticity measurement method based on the spheroidization process of non-spherical shaped cell","volume":"21","year":"2021","journal-title":"Sensors"},{"key":"2024070320505977700_c42","doi-asserted-by":"publisher","first-page":"1774","DOI":"10.1091\/mbc.E19-01-0027","article-title":"Mechanical stress triggers nuclear remodeling and the formation of transmembrane actin nuclear lines with associated nuclear pore complexes","volume":"31","year":"2020","journal-title":"Mol. Biol. Cell"},{"key":"2024070320505977700_c43","doi-asserted-by":"publisher","first-page":"eaba2894","DOI":"10.1126\/science.aba2894","article-title":"The nucleus acts as a ruler tailoring cell responses to spatial constraints","volume":"370","year":"2020","journal-title":"Science"},{"key":"2024070320505977700_c44","doi-asserted-by":"publisher","first-page":"38063","DOI":"10.1038\/srep38063","article-title":"The mammalian LINC complex regulates genome transcriptional responses to substrate rigidity","volume":"6","year":"2016","journal-title":"Sci. Rep."},{"key":"2024070320505977700_c45","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1016\/j.bpj.2010.04.011","article-title":"Actomyosin tension exerted on the nucleus through nesprin-1 connections influences endothelial cell adhesion, migration, and cyclic strain-induced reorientation","volume":"99","year":"2010","journal-title":"Biophys. J."},{"key":"2024070320505977700_c46","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1111\/j.1365-2818.1989.tb00586.x","article-title":"Axial resolution of confocal fluorescence microscopy","volume":"154","year":"1989","journal-title":"J. Microsc."},{"key":"2024070320505977700_c47","doi-asserted-by":"publisher","first-page":"prot5255","DOI":"10.1101\/pdb.prot5255","article-title":"Adhesive micropatterns for cells: A microcontact printing protocol","volume":"2009","journal-title":"Cold Spring Harbor Protoc."},{"key":"2024070320505977700_c48","doi-asserted-by":"publisher","first-page":"10997","DOI":"10.1038\/ncomms10997","article-title":"Perinuclear Arp2\/3-driven actin polymerization enables nuclear deformation to facilitate cell migration through complex environments","volume":"7","year":"2016","journal-title":"Nat. Commun."}],"container-title":["APL Bioengineering"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.aip.org\/aip\/apb\/article-pdf\/doi\/10.1063\/5.0071652\/20031609\/010901_1_5.0071652.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/pubs.aip.org\/aip\/apb\/article-pdf\/doi\/10.1063\/5.0071652\/20031609\/010901_1_5.0071652.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.aip.org\/aip\/apb\/article-pdf\/doi\/10.1063\/5.0071652\/20031609\/010901_1_5.0071652.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,22]],"date-time":"2025-04-22T20:07:26Z","timestamp":1745352446000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.aip.org\/apb\/article\/6\/1\/010901\/2820296\/Viscous-shaping-of-the-compliant-cell-nucleus"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,4]]},"references-count":48,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2022,3,1]]}},"URL":"https:\/\/doi.org\/10.1063\/5.0071652","relation":{},"ISSN":["2473-2877"],"issn-type":[{"value":"2473-2877","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2022,3,1]]},"published":{"date-parts":[[2022,1,4]]},"article-number":"010901"}}