Chromatin phase separation and nuclear shape fluctuations are correlated in a polymer model of the nucleus

References

• Mirny LA, Imakaev M, Abdennur N. Two major mechanisms of chromosome organization. Curr Opin Cell Biol. 2019;58:142–20. doi:10.1016/j.ceb.2019.05.001
   PubMed Web of Science ®Google Scholar
• Jost D, Carrivain P, Cavalli G, et al. Modeling epigenome folding: formation and dynamics of topologically associated chromatin domains. Nucleic Acids Res. 2014;42(15):9553–9561. doi: 10.1093/nar/gku698
   PubMed Web of Science ®Google Scholar
• Bajpai G, Amiad Pavlov D, Lorber D, et al. Mesoscale phase separation of chromatin in the nucleus. Elife. 2021;10:e63976. doi:10.7554/eLife.63976
   PubMed Web of Science ®Google Scholar
• Amiad-Pavlov D, Lorber D, Bajpai G, et al. Live imaging of chromatin distribution reveals novel principles of nuclear architecture and chromatin compartmentalization. Sci Adv. 2021;7(23):eabf6251. doi: 10.1126/sciadv.abf6251
   PubMed Web of Science ®Google Scholar
• Falk M, Feodorova Y, Naumova N, et al. Heterochromatin drives compartmentalization of inverted and conventional nuclei. Nature. 2019;570(7761):395–399. doi: 10.1038/s41586-019-1275-3
   PubMed Web of Science ®Google Scholar
• Cremer T, Cremer M, Hübner B, et al. The 4D nucleome: evidence for a dynamic nuclear landscape based on co-aligned active and inactive nuclear compartments. FEBS Lett. 2015;589(20PartA):2931–2943. doi: 10.1016/j.febslet.2015.05.037
   PubMedGoogle Scholar
• Szabo Q, Bantignies F, Cavalli G. Principles of genome folding into topologically associating domains. Sci Adv. 2019;5(4):eaaw1668. doi: 10.1126/sciadv.aaw1668
   PubMed Web of Science ®Google Scholar
• Solovei I, Thanisch K, Feodorova Y. How to rule the nucleus: divide et impera. Curr Opin Cell Biol. 2016;40:47–59. doi:10.1016/j.ceb.2016.02.014
   PubMed Web of Science ®Google Scholar
• Sanulli S, Narlikar G. Liquid-like interactions in heterochromatin: implications for mechanism and regulation. Curr Opin Cell Biol. 2020;64:90–96. doi:10.1016/j.ceb.2020.03.004
   PubMed Web of Science ®Google Scholar
• Hildebrand EM, Dekker J. Mechanisms and functions of chromosome compartmentalization. Trends Biochem Sci. 2020;45(5):385–396. doi: 10.1016/j.tibs.2020.01.002
   PubMed Web of Science ®Google Scholar
• Gorkin DU, Leung D, Ren B. The 3D Genome in Transcriptional Regulation and pluripotency. Cell Stem Cell. 2014;14(6):762–775. doi: 10.1016/j.stem.2014.05.017
   PubMed Web of Science ®Google Scholar
• Zheng H, Xie W. The role of 3D genome organization in development and cell differentiation. Nat Rev Mol Cell Biol. 2019;20(9):535–550. doi: 10.1038/s41580-019-0132-4
   PubMed Web of Science ®Google Scholar
• Bonev B, Cavalli G. Organization and function of the 3D genome. Nat Rev Genet. 2016;17(11):661–678. doi: 10.1038/nrg.2016.112
   PubMed Web of Science ®Google Scholar
• Kubben N, Adriaens M, Meuleman W, et al. Mapping of lamin A- and progerin-interacting genome regions. Chromosoma. 2012;121(5):447–464. doi: 10.1007/s00412-012-0376-7
   PubMed Web of Science ®Google Scholar
• San Martin R, Das P, Dos Reis Marques R, et al. Chromosome compartmentalization alterations in prostate cancer cell lines model disease progression. J Cell Bio. 2021;221(2):e202104108. doi: 10.1083/jcb.202104108
   PubMed Web of Science ®Google Scholar
• Zhou Y, Gerrard DL, Wang J, et al. Temporal dynamic reorganization of 3D chromatin architecture in hormone-induced breast cancer and endocrine resistance. Nat Commun. 2019;10(1):1522. doi: 10.1038/s41467-019-09320-9
   PubMedGoogle Scholar
• Barutcu AR, Lajoie BR, McCord RP, et al. Chromatin interaction analysis reveals changes in small chromosome and telomere clustering between epithelial and breast cancer cells. Genome Biol. 2015;16(1):214. doi: 10.1186/s13059-015-0768-0
   PubMedGoogle Scholar
• Butin-Israeli V, Adam SA, Goldman AE, et al. Nuclear lamin functions and disease. Trends Genet. 2012;28(9):464–471. doi: 10.1016/j.tig.2012.06.001
   PubMed Web of Science ®Google Scholar
• Misteli T. Higher-order genome organization in human disease. Cold Spring Harb Perspect Biol. 2010;2(8):a000794. doi: 10.1101/cshperspect.a000794
   PubMed Web of Science ®Google Scholar
• Stephens AD, Banigan EJ, Marko JF. Chromatin’s physical properties shape the nucleus and its functions. Curr Opin Cell Biol. 2019;58:76–84. doi:10.1016/j.ceb.2019.02.006
   PubMed Web of Science ®Google Scholar
• Stephens AD, Liu PZ, Banigan EJ, et al. Chromatin histone modifications and rigidity affect nuclear morphology independent of lamins. Mol Biol Cell. 2018;29(2):220–233. doi: 10.1091/mbc.E17-06-0410
   PubMed Web of Science ®Google Scholar
• Samwer M, Schneider MWG, Hoefler R, et al. DNA cross-bridging shapes a single nucleus from a set of mitotic chromosomes. Cell. 2017;170(5):956–972.e23. doi: 10.1016/j.cell.2017.07.038
   PubMed Web of Science ®Google Scholar
• Furusawa T, Rochman M, Taher L, et al. Chromatin decompaction by the nucleosomal binding protein HMGN5 impairs nuclear sturdiness. Nat Commun. 2015;6(1):6138. doi: 10.1038/ncomms7138
   PubMedGoogle Scholar
• Wang P, Dreger M, Madrazo E, et al. WDR5 modulates cell motility and morphology and controls nuclear changes induced by a 3D environment. Proc Natl Acad Sci. 2018;115(34):8581–8586. doi: 10.1073/pnas.1719405115
   PubMed Web of Science ®Google Scholar
• Kalukula Y, Stephens AD, Lammerding J, et al. Mechanics and functional consequences of nuclear deformations. Nat Rev Mol Cell Biol. 2022;23(9):583–602. doi: 10.1038/s41580-022-00480-z
   PubMed Web of Science ®Google Scholar
• Allis CD, Jenuwein T. The molecular hallmarks of epigenetic control. Nat Rev Genet. 2016;17(8):487–500. doi: 10.1038/nrg.2016.59
   PubMed Web of Science ®Google Scholar
• Rowley MJ, Nichols MH, Lyu X, et al. Evolutionarily conserved principles predict 3D chromatin organization. Mol Cell. 2017;67(5):837–852.e7. doi: 10.1016/j.molcel.2017.07.022
   PubMed Web of Science ®Google Scholar
• Solovei I, Kreysing M, Lanctôt C, et al. Nuclear architecture of rod photoreceptor cells adapts to Vision in Mammalian Evolution. Cell. 2009;137(2):356–368. doi: 10.1016/j.cell.2009.01.052
   PubMed Web of Science ®Google Scholar
• Stephens AD, Banigan EJ, Adam SA, et al. Chromatin and lamin a determine two different mechanical response regimes of the cell nucleus. Mol Biol Cell. 2017;28(14):1984–1996. doi: 10.1091/mbc.e16-09-0653
   PubMed Web of Science ®Google Scholar
• Shimamoto Y, Tamura S, Masumoto H, et al. Nucleosome–nucleosome interactions via histone tails and linker DNA regulate nuclear rigidity. Mol Biol Cell. 2017;28(11):1580–1589. doi: 10.1091/mbc.e16-11-0783
   PubMed Web of Science ®Google Scholar
• Ghosh S, Cuevas VC, Seelbinder B, et al. Image-based elastography of Heterochromatin and Euchromatin Domains in the deforming cell nucleus. Small Weinh Bergstr Ger. 2021;17(5):e2006109. doi: 10.1002/smll.202006109
   PubMed Web of Science ®Google Scholar
• Brunet A, Destainville N, Collas P. Physical constraints in polymer modeling of chromatin associations with the nuclear periphery at kilobase scale. Nucleus. 2021;12(1):6–20. doi: 10.1080/19491034.2020.1868105
   PubMed Web of Science ®Google Scholar
• Girard M, Cruz MO, de la Marko JF, et al. Heterochromatin flexibility contributes to chromosome segregation in the cell nucleus. 2020. doi: 10.1101/2020.12.01.403832
   Google Scholar
• Cook PR, Marenduzzo D. Entropic organization of interphase chromosomes. J Cell Bio. 2009;186(6):825–834. doi: 10.1083/jcb.200903083
   PubMed Web of Science ®Google Scholar
• Adame-Arana O, Bajpai G, Lorber D, et al. Regulation of chromatin microphase separation by binding of protein complexes. Elife. 2023;12:e82983. doi:10.7554/eLife.82983
   PubMedGoogle Scholar
• Di Pierro M, Zhang B, Aiden EL, et al. Transferable model for chromosome architecture. Proc Natl Acad Sci. 2016;113(43):12168–12173. doi: 10.1073/pnas.1613607113
   PubMed Web of Science ®Google Scholar
• Stephens AD, Liu PZ, Kandula V, et al. Physicochemical mechanotransduction alters nuclear shape and mechanics via heterochromatin formation. Mol Biol Cell. 2019;30(17):2320–2330. doi: 10.1091/mbc.E19-05-0286
   PubMed Web of Science ®Google Scholar
• Xia Y, Ivanovska IL, Zhu K, et al. Nuclear rupture at sites of high curvature compromises retention of DNA repair factors. J Cell Bio. 2018;217(11):3796–3808. doi: 10.1083/jcb.201711161
   PubMed Web of Science ®Google Scholar
• Strom AR, Emelyanov AV, Mir M, et al. Phase separation drives heterochromatin domain formation. Nature. 2017;547(7662):241–245. doi: 10.1038/nature22989
   PubMed Web of Science ®Google Scholar
• Larson AG, Elnatan D, Keenen MM, et al. Liquid droplet formation by HP1α suggests a role for phase separation in heterochromatin. Nature. 2017;547(7662):236–240. doi: 10.1038/nature22822
   PubMed Web of Science ®Google Scholar
• Strom AR, Biggs RJ, Banigan EJ, et al. HP1α is a chromatin crosslinker that controls nuclear and mitotic chromosome mechanics. Elife. 2021;10:e63972. doi: 10.7554/eLife.63972
   PubMed Web of Science ®Google Scholar
• Solovei I, Wang A, Thanisch K, et al. LBR and lamin A/C sequentially tether peripheral heterochromatin and inversely regulate differentiation. Cell. 2013;152(3):584–598. doi: 10.1016/j.cell.2013.01.009
   PubMed Web of Science ®Google Scholar
• Goldman RD, Shumaker DK, Erdos MR, et al. Accumulation of mutant lamin a causes progressive changes in nuclear architecture in Hutchinson–Gilford progeria syndrome. Proc Natl Acad Sci. 2004;101(24):8963–8968. doi: 10.1073/pnas.0402943101
   PubMed Web of Science ®Google Scholar
• Taimen P, Pfleghaar K, Shimi T, et al. A progeria mutation reveals functions for lamin a in nuclear assembly, architecture, and chromosome organization. Proc Natl Acad Sci U S A. 2009;106(49):20788–20793. doi: 10.1073/pnas.0911895106
   PubMed Web of Science ®Google Scholar
• Haithcock E, Dayani Y, Neufeld E, et al. Age-related changes of nuclear architecture in caenorhabditis elegans. Proc Natl Acad Sci. 2005;102(46):16690–16695. doi: 10.1073/pnas.0506955102
   PubMed Web of Science ®Google Scholar
• Hoskins VE, Smith K, Reddy KL. The shifting shape of genomes: dynamics of Heterochromatin Interactions at the Nuclear Lamina. Curr Opin Genet Dev. 2021;67:163–173. doi:10.1016/j.gde.2021.02.003
   PubMed Web of Science ®Google Scholar
• Harr JC, Luperchio TR, Wong X, et al. Directed targeting of chromatin to the nuclear lamina is mediated by chromatin state and A-type lamins. J Cell Bio. 2015;208(1):33–52. doi: 10.1083/jcb.201405110
   PubMed Web of Science ®Google Scholar
• Zheng X, Hu J, Yue S, et al. Lamins organize the global three-dimensional genome from the nuclear periphery. Mol Cell. 2018;71(5):802–815.e7. doi: 10.1016/j.molcel.2018.05.017
   PubMed Web of Science ®Google Scholar
• van Steensel B, Belmont AS. Lamina-Associated Domains: links with chromosome architecture, Heterochromatin, and gene repression. Cell. 2017;169(5):780–791. doi: 10.1016/j.cell.2017.04.022
   PubMed Web of Science ®Google Scholar
• Poleshko A, Mansfield K, Burlingame C, et al. The human protein PRR14 tethers heterochromatin to the nuclear lamina during interphase and mitotic exit. Cell Rep. 2013;5(2):292–301. doi: 10.1016/j.celrep.2013.09.024
   PubMed Web of Science ®Google Scholar
• Schreiner SM, Koo PK, Zhao Y, et al. The tethering of chromatin to the nuclear envelope supports nuclear mechanics. Nat Commun. 2015;6(1):7159. doi: 10.1038/ncomms8159
   PubMedGoogle Scholar
• Brahmachari S, Contessoto VG, Di Pierro M, et al. Shaping the genome via lengthwise compaction, phase separation, and lamina adhesion. Nucleic Acids Res. 2022;50(8):4258–4271. doi: 10.1093/nar/gkac231
   PubMed Web of Science ®Google Scholar
• Laghmach R, Di Pierro M, Potoyan DA. The interplay of chromatin phase separation and lamina interactions in nuclear organization. Biophys J. 2021;120(22):5005–5017. doi: 10.1016/j.bpj.2021.10.012
   PubMed Web of Science ®Google Scholar
• Barbieri M, Chotalia M, Fraser J, et al. Complexity of chromatin folding is captured by the strings and binders switch model. Proc Natl Acad Sci. 2012;109(40):16173–16178. doi: 10.1073/pnas.1204799109
   PubMed Web of Science ®Google Scholar
• di Stefano M, Nützmann H-W, Marti-Renom MA, et al. Polymer modelling unveils the roles of heterochromatin and nucleolar organizing regions in shaping 3D genome organization in Arabidopsis thaliana. Nucleic Acids Res. 2021;49(4):1840–1858. doi: 10.1093/nar/gkaa1275
   PubMed Web of Science ®Google Scholar
• Lao Z, Kamat K, Jiang Z, et al. OpenNucleome for high resolution nuclear structural and dynamical modeling. Elife. 2024;13:e93223.1 doi:10.7554/eLife.93223.1.
   Google Scholar
• Kamat K, Lao Z, Qi Y, et al. Compartmentalization with nuclear landmarks yields random, yet precise, genome organization. Biophys J. 2023;122(7):1376–1389. doi: 10.1016/j.bpj.2023.03.003
   PubMedGoogle Scholar
• Banigan EJ, Stephens AD, Marko JF. Mechanics and buckling of biopolymeric shells and cell nuclei. Biophys J. 2017;113(8):1654–1663. doi: 10.1016/j.bpj.2017.08.034
   PubMed Web of Science ®Google Scholar
• Lionetti MC, Bonfanti S, Fumagalli MR, et al. Chromatin and cytoskeletal tethering determine nuclear morphology in progerin-expressing cells. Biophys J. 2020;118(9):2319–2332. doi: 10.1016/j.bpj.2020.04.001
   PubMed Web of Science ®Google Scholar
• Kremer K, Grest GS. Dynamics of entangled linear polymer melts: a molecular-dynamics simulation. J Chem Phys. 1990;92(8):5057–5086. doi: 10.1063/1.458541
   Web of Science ®Google Scholar
• Schwarzer W, Abdennur N, Goloborodko A, et al. Two independent modes of chromatin organization revealed by cohesin removal. Nature. 2017;551(7678):51–56. doi: 10.1038/nature24281
   PubMed Web of Science ®Google Scholar
• Wutz G, Várnai C, Nagasaka K, et al. Topologically associating domains and chromatin loops depend on cohesin and are regulated by CTCF, WAPL, and PDS5 proteins. Embo J. 2017;36(24):3573–3599. doi: 10.15252/embj.201798004
   PubMed Web of Science ®Google Scholar
• Lieberman-Aiden E, van Berkum NL, Williams L, et al. Comprehensive mapping of long-range interactions reveals folding principles of the human genome. Science. 2009;326(5950):289–293. doi: 10.1126/science.1181369
   PubMed Web of Science ®Google Scholar
• Rosa A, Everaers R, Henikoff S. Structure and dynamics of Interphase Chromosomes. PLoS Comput Biol. 2008;4(8):e1000153. doi: 10.1371/journal.pcbi.1000153
   PubMed Web of Science ®Google Scholar
• Shimi T, Pfleghaar K, Kojima S-I, et al. The A- and B-type nuclear lamin networks: microdomains involved in chromatin organization and transcription. Genes Dev. 2008;22(24):3409–3421. doi: 10.1101/gad.1735208
   PubMed Web of Science ®Google Scholar
• Plimpton S. Fast parallel algorithms for Short-Range Molecular Dynamics. J Comput Phys. 1995;117(1):1–19. doi: 10.1006/jcph.1995.1039
   Web of Science ®Google Scholar
• Patteson AE, Vahabikashi A, Pogoda K, et al. Vimentin protects cells against nuclear rupture and DNA damage during migration. J Cell Bio. 2019;218(12):4079–4092. doi: 10.1083/jcb.201902046
   PubMed Web of Science ®Google Scholar
• Liu K, Patteson AE, Banigan EJ, et al. Dynamic nuclear structure emerges from chromatin cross-links and motors. Phys Rev Lett. 2021;126(15):158101. doi: 10.1103/PhysRevLett.126.158101
   PubMed Web of Science ®Google Scholar
• Harris CR, Millman KJ, van der Walt SJ, et al. Array programming with NumPy. Nature. 2020;585(7825):357–362. doi: 10.1038/s41586-020-2649-2
   PubMed Web of Science ®Google Scholar
• Biswas A, Munoz O, Kim K. et al. Conserved nucleocytoplasmic density homeostasis drives cellular organization across eukaryotes. 2023. doi: 10.1101/2023.09.05.556409
   Google Scholar
• Mazumder A, Roopa T, Basu A, et al. Dynamics of chromatin decondensation reveals the structural integrity of a mechanically prestressed nucleus. Biophys J. 2008;95(6):3028–3035. doi: 10.1529/biophysj.108.132274
   PubMed Web of Science ®Google Scholar
• Neubert E, Meyer D, Rocca F, et al. Chromatin swelling drives neutrophil extracellular trap release. Nat Commun. 2018;9(1):3767. doi: 10.1038/s41467-018-06263-5
   PubMedGoogle Scholar
• Kim K, Guck J. The relative densities of cytoplasm and Nuclear Compartments Are Robust against strong perturbation. Biophys J. 2020;119(10):1946–1957. doi: 10.1016/j.bpj.2020.08.044
   PubMed Web of Science ®Google Scholar
• Olins AL, Gould TJ, Boyd L, et al. Hyperosmotic stress: in situ chromatin phase separation. Nucleus. 2020;11(1):1–18. doi: 10.1080/19491034.2019.1710321
   PubMed Web of Science ®Google Scholar
• Albiez H, Cremer M, Tiberi C, et al. Chromatin domains and the interchromatin compartment form structurally defined and functionally interacting nuclear networks. Chromosome Res. 2006;14(7):707–733. doi: 10.1007/s10577-006-1086-x
   PubMed Web of Science ®Google Scholar
• Irianto J, Swift J, Martins R, et al. Osmotic challenge drives rapid and reversible chromatin condensation in chondrocytes. Biophys J. 2013;104(4):759–769. doi: 10.1016/j.bpj.2013.01.006
   PubMed Web of Science ®Google Scholar
• Strickfaden H, Tolsma TO, Sharma A, et al. Condensed chromatin behaves like a solid on the mesoscale in vitro and in living cells. Cell. 2020;183(7):1772–1784.e13. doi: 10.1016/j.cell.2020.11.027
   PubMed Web of Science ®Google Scholar
• Chu F-Y, Haley SC, Zidovska A. On the origin of shape fluctuations of the cell nucleus. Proc Natl Acad Sci. 2017;114(39):10338–10343. doi: 10.1073/pnas.1702226114
   PubMed Web of Science ®Google Scholar
• Wang L, Gao Y, Zheng X, et al. Histone modifications regulate chromatin compartmentalization by contributing to a phase separation mechanism. Mol Cell. 2019;76(4):646–659.e6. doi: 10.1016/j.molcel.2019.08.019
   PubMed Web of Science ®Google Scholar
• Xu J, Ma H, Jin J, et al. Super-resolution imaging of higher-order chromatin structures at different epigenomic states in Single Mammalian Cells. Cell Rep. 2018;24(4):873–882. doi: 10.1016/j.celrep.2018.06.085
   PubMed Web of Science ®Google Scholar
• Gibson BA, Doolittle LK, Schneider MWG, et al. Organization of chromatin by intrinsic and regulated phase separation. Cell. 2019;179(2):470–484.e21. doi: 10.1016/j.cell.2019.08.037
   PubMed Web of Science ®Google Scholar
• Kiseleva AA, Cheng Y-C, Smith CL, et al. PRR14 organizes H3K9me3-modified heterochromatin at the nuclear lamina. Nucleus. 2023;14(1):2165602. doi: 10.1080/19491034.2023.2165602
   PubMed Web of Science ®Google Scholar
• Poleshko A, Smith CL, Nguyen SC, et al. H3K9me2 orchestrates inheritance of spatial positioning of peripheral heterochromatin through mitosis. Elife. 2019;8:e49278. doi: 10.7554/eLife.49278
   PubMed Web of Science ®Google Scholar
• Lammerding J, Hsiao J, Schulze PC, et al. Abnormal nuclear shape and impaired mechanotransduction in emerin-deficient cells. J Cell Bio. 2005;170(5):781–791. doi: 10.1083/jcb.200502148
   PubMed Web of Science ®Google Scholar
• Carvajal AS, McKenna T, Arzt EW, et al. Overexpression of lamin B receptor results in impaired skin differentiation. PLoS One. 2015;10(6):e0128917. doi: 10.1371/journal.pone.0128917
   PubMed Web of Science ®Google Scholar
• Olins AL, Rhodes G, Welch DBM, et al. Lamin B receptor. Nucleus. 2010;1(1):53–70. doi: 10.4161/nucl.1.1.10515
   PubMed Web of Science ®Google Scholar
• Lammerding J, Fong LG, Ji JY, et al. Lamins a and C but not lamin B1 regulate nuclear Mechanics*. J Biol Chem. 2006;281(35):25768–25780. doi: 10.1074/jbc.M513511200
   PubMed Web of Science ®Google Scholar
• Bercht Pfleghaar K, Taimen P, Butin-Israeli V, et al. Gene-rich chromosomal regions are preferentially localized in the lamin B deficient nuclear blebs of atypical progeria cells. Nucleus. 2015;6(1):66–76. doi: 10.1080/19491034.2015.1004256
   PubMed Web of Science ®Google Scholar
• Berg IK, Currey ML, Gupta S, et al. Transcription inhibition suppresses nuclear blebbing and rupture independent of nuclear rigidity. J Cell Sci. 2023;136(20). doi: 10.1242/jcs.261547
   PubMed Web of Science ®Google Scholar
• Nava MM, Miroshnikova YA, Biggs LC, et al. Heterochromatin-driven nuclear softening protects the genome against mechanical stress-induced damage. Cell. 2020;181(4):800–817.e22. doi: 10.1016/j.cell.2020.03.052
   PubMed Web of Science ®Google Scholar
• Finan JD, Leddy HA, Guilak F. Osmotic stress alters chromatin condensation and nucleocytoplasmic transport. Biochem Biophys Res Commun. 2011;408(2):230–235. doi: 10.1016/j.bbrc.2011.03.131
   PubMed Web of Science ®Google Scholar
• Khavari A, Ehrlicher AJ, Aegerter CM. Nuclei deformation reveals pressure distributions in 3D cell clusters. PLoS One. 2019;14(9):e0221753. doi: 10.1371/journal.pone.0221753
   PubMed Web of Science ®Google Scholar
• Finan JD, Chalut KJ, Wax A, et al. Nonlinear osmotic properties of the cell nucleus. Ann Biomed Eng. 2009;37(3):477–491. doi: 10.1007/s10439-008-9618-5
   PubMed Web of Science ®Google Scholar
• Swift J, Ivanovska IL, Buxboim A, et al. Nuclear lamin-A scales with tissue stiffness and enhances matrix-directed differentiation. Science. 2013;341(6149):1240104. doi: 10.1126/science.1240104
   PubMed Web of Science ®Google Scholar
• Pajerowski JD, Dahl KN, Zhong FL, et al. Physical plasticity of the nucleus in stem cell differentiation. Proc Natl Acad Sci. 2007;104(40):15619–15624. doi: 10.1073/pnas.0702576104
   PubMed Web of Science ®Google Scholar
• Lammerding J, Schulze PC, Takahashi T, et al. Lamin A/C deficiency causes defective nuclear mechanics and mechanotransduction. J Clin Invest. 2004;113(3):370–378. doi: 10.1172/JCI200419670
   PubMed Web of Science ®Google Scholar
• Mattout A, Pike B, Towbin B, et al. An EDMD Mutation in C. elegans lamin blocks muscle-specific gene relocation and compromises muscle integrity. Curr Biol. 2011;21(19):1603–1614. doi: 10.1016/j.cub.2011.08.030
   PubMed Web of Science ®Google Scholar
• Introini V, Kidiyoor GR, Porcella G, et al. Centripetal nuclear shape fluctuations associate with chromatin condensation in early prophase. Commun Biol. 2023;6(1):1–11. doi: 10.1038/s42003-023-05074-9
   PubMed Web of Science ®Google Scholar
• Hoffmann K, Dreger CK, Olins AL, et al. Mutations in the gene encoding the lamin B receptor produce an altered nuclear morphology in granulocytes (pelger–huët anomaly). Nat Genet. 2002;31(4):410–414. doi: 10.1038/ng925
   PubMed Web of Science ®Google Scholar
• Zwerger M, Herrmann H, Gaines P, et al. Granulocytic nuclear differentiation of lamin B receptor–deficient mouse EPRO cells. Exp Hematol. 2008;36(8):977–987. doi: 10.1016/j.exphem.2008.03.003
   PubMed Web of Science ®Google Scholar
• Shultz LD, Lyons BL, Burzenski LM, et al. Mutations at the mouse ichthyosis locus are within the lamin B receptor gene: a single gene model for human pelger–huët anomaly. Hum Mol Genet. 2003;12(1):61–69. doi: 10.1093/hmg/ddg003
   PubMed Web of Science ®Google Scholar
• Olins AL, Herrmann H, Lichter P, et al. Nuclear envelope and chromatin compositional differences comparing undifferentiated and retinoic acid- and Phorbol Ester-Treated HL-60 Cells. Exp Cell Res. 2001;268(2):115–127. doi: 10.1006/excr.2001.5269
   PubMed Web of Science ®Google Scholar
• Olins AL, Olins DE. Cytoskeletal influences on nuclear shape in granulocytic HL-60 cells. BMC Cell Biol. 2004;5(1):30. doi: 10.1186/1471-2121-5-30
   PubMedGoogle Scholar
• Cohen TV, Klarmann KD, Sakchaisri K, et al. The lamin B receptor under transcriptional control of C/EBPε is required for morphological but not functional maturation of neutrophils. Hum Mol Genet. 2008;17(19):2921–2933. doi: 10.1093/hmg/ddn191
   PubMed Web of Science ®Google Scholar
• Larrieu D, Britton S, Demir M, et al. Chemical inhibition of NAT10 corrects defects of laminopathic cells. Science. 2014;344(6183):527–532. doi: 10.1126/science.1252651
   PubMed Web of Science ®Google Scholar
• Hatch EM, Hetzer MW. Nuclear envelope rupture is induced by actin-based nucleus confinement. J Cell Bio. 2016;215(1):27–36. doi: 10.1083/jcb.201603053
   PubMed Web of Science ®Google Scholar
• Mistriotis P, Wisniewski EO, Bera K, et al. Confinement hinders motility by inducing RhoA-mediated nuclear influx, volume expansion, and blebbing. J Cell Bio. 2019;218(12):4093–4111. doi: 10.1083/jcb.201902057
   PubMed Web of Science ®Google Scholar
• Pho M, Berrada Y., Gunda A., et al. Actin contraction controls nuclear blebbing and rupture independent of actin confinement. 2022. doi: 10.1101/2022.12.01.518663
   Google Scholar
• Hobson CM, Kern M, O’Brien ET, et al. Correlating nuclear morphology and external force with combined atomic force microscopy and light sheet imaging separates roles of chromatin and lamin A/C in nuclear mechanics. Mol Biol Cell. 2020;31(16):1788–1801. doi: 10.1091/mbc.E20-01-0073
   PubMed Web of Science ®Google Scholar
• Chalut KJ, Höpfler M, Lautenschläger F, et al. Chromatin decondensation and nuclear softening accompany nanog downregulation in embryonic stem cells. Biophys J. 2012;103(10):2060–2070. doi: 10.1016/j.bpj.2012.10.015
   PubMed Web of Science ®Google Scholar
• Yuan F, Alimohamadi H, Bakka B, et al. Membrane bending by protein phase separation. Proc Natl Acad Sci. 2021;118(11):e2017435118. doi: 10.1073/pnas.2017435118
   PubMed Web of Science ®Google Scholar
• Lee Y, Park S, Yuan F, et al. Transmembrane coupling of liquid-like protein condensates. Nat Commun. 2023;14(1):8015. doi: 10.1038/s41467-023-43332-w
   PubMed Web of Science ®Google Scholar
• Kusumaatmaja H, May AI, Feeney M, et al. Wetting of phase-separated droplets on plant vacuole membranes leads to a competition between tonoplast budding and nanotube formation. Proc Natl Acad Sci. 2021;118(36):e2024109118. doi: 10.1073/pnas.2024109118
   PubMed Web of Science ®Google Scholar
• Bergeron-Sandoval L-P, Michnick SWM. Mechanics, structure and function of biopolymer condensates. J Mol Biol. 2018;430(23):4754–4761. doi: 10.1016/j.jmb.2018.06.023
   PubMed Web of Science ®Google Scholar
• Kusumaatmaja H, Lipowsky R. Droplet-induced budding transitions of membranes. Soft Matter. 2011;7(15):6914–6919. doi: 10.1039/c1sm05499f
   Web of Science ®Google Scholar
• Quail T, Golfier S, Elsner M, et al. Force generation by protein–DNA co-condensation. Nat Phys. 2021;17(9):1007–1012. doi: 10.1038/s41567-021-01285-1
   Web of Science ®Google Scholar
• Strom AR, Kim Y., Zhao H., et al. Condensate-driven interfacial forces reposition DNA loci and measure chromatin viscoelasticity. 2023. doi: 10.1101/2023.02.27.530281
   Google Scholar
• Shin Y, Chang Y-C, Lee DSW, et al. Liquid nuclear condensates mechanically sense and restructure the genome. Cell. 2018;175(6):1481–1491.e13. doi: 10.1016/j.cell.2018.10.057
   PubMed Web of Science ®Google Scholar
• Leibler L. Theory of microphase separation in block copolymers. Macromolecules. 1980;13(6):1602–1617. doi: 10.1021/ma60078a047
   Web of Science ®Google Scholar
• Swift BW, de la Cruz MO. Random copolymers in concentrated solutions. Europhys Lett. 1996;35(7):487. doi: 10.1209/epl/i1996-00140-7
   Google Scholar
• Conte M, Fiorillo L, Bianco S, et al. Polymer physics indicates chromatin folding variability across single-cells results from state degeneracy in phase separation. Nat Commun. 2020;11(1):3289. doi: 10.1038/s41467-020-17141-4
   PubMed Web of Science ®Google Scholar
• Conte M, Irani E, Chiariello AM, et al. Loop-extrusion and polymer phase-separation can co-exist at the single-molecule level to shape chromatin folding. Nat Commun. 2022;13(1):4070. doi: 10.1038/s41467-022-31856-6
   PubMed Web of Science ®Google Scholar
• Michieletto D, Colì D, Marenduzzo D, et al. Nonequilibrium theory of epigenomic microphase separation in the Cell Nucleus. Phys Rev Lett. 2019;123(22):228101. doi: 10.1103/PhysRevLett.123.228101
   PubMed Web of Science ®Google Scholar