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Nuclear blebs (i.e. herniations of the nuclear envelope) can be induced by (1) nuclear compression, (2) nuclear migration (e.g. cancer metastasis), (3) actin contraction, (4) lamin mutation or depletion, and (5) heterochromatin enzyme inhibition. Recent work has shown that chromatin transformation is a hallmark of bleb formation, but the transformation of higher-order structures in blebs is not well understood. As higher-order chromatin has been shown to assemble into nanoscopic packing domains, we investigated whether (1) packing domain organization is altered within nuclear blebs and (2) whether alteration in packing domain structure contributed to bleb formation. Using dual-partial wave spectroscopic microscopy, we show that chromatin-packing domains within blebs are transformed both by B-type lamin depletion and the inhibition of heterochromatin enzymes compared to what is seen in the nuclear body. Pairing these results with single-molecule localization microscopy of constitutive heterochromatin, we show fragmentation of nanoscopic heterochromatin domains within bleb domains. Overall, these findings indicate that chromatin within blebs is associated with a fragmented higher-order chromatin structure.<\/jats:p>","DOI":"10.1242\/jcs.262161","type":"journal-article","created":{"date-parts":[[2025,1,29]],"date-time":"2025-01-29T05:16:12Z","timestamp":1738127772000},"source":"Crossref","is-referenced-by-count":13,"title":["Nuclear blebs are associated with destabilized chromatin-packing domains"],"prefix":"10.1242","volume":"138","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3520-835X","authenticated-orcid":false,"given":"Emily M.","family":"Pujadas Liwag","sequence":"first","affiliation":[{"name":"Northwestern University 1 Department of Biomedical Engineering , , Evanston, IL 60208 ,","place":["USA"]},{"name":"Northwestern University 2 IBIS Interdisciplinary Biological Sciences Graduate Program , , Evanston, IL 60208 ,","place":["USA"]},{"name":"Center for Physical Genomics and Engineering, Northwestern University 3 , Evanston, IL 60208 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-9278-7491","authenticated-orcid":false,"given":"Nicolas","family":"Acosta","sequence":"additional","affiliation":[{"name":"Northwestern University 1 Department of Biomedical Engineering , , Evanston, IL 60208 ,","place":["USA"]},{"name":"Center for Physical Genomics and Engineering, Northwestern University 3 , Evanston, IL 60208 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9355-7681","authenticated-orcid":false,"given":"Luay Matthew","family":"Almassalha","sequence":"additional","affiliation":[{"name":"Northwestern University 1 Department of Biomedical Engineering , , Evanston, IL 60208 ,","place":["USA"]},{"name":"Center for Physical Genomics and Engineering, Northwestern University 3 , Evanston, IL 60208 ,","place":["USA"]},{"name":"Northwestern Memorial Hospital 4 Department of Gastroenterology and Hepatology , , Chicago, IL 60611 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1110-2822","authenticated-orcid":false,"given":"Yuanzhe (Patrick)","family":"Su","sequence":"additional","affiliation":[{"name":"Northwestern University 1 Department of Biomedical Engineering , , Evanston, IL 60208 ,","place":["USA"]},{"name":"Center for Physical Genomics and Engineering, Northwestern University 3 , Evanston, IL 60208 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-1008-2844","authenticated-orcid":false,"given":"Ruyi","family":"Gong","sequence":"additional","affiliation":[{"name":"Northwestern University 1 Department of Biomedical Engineering , , Evanston, IL 60208 ,","place":["USA"]},{"name":"Center for Physical Genomics and Engineering, Northwestern University 3 , Evanston, IL 60208 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7657-1649","authenticated-orcid":false,"given":"Masato T.","family":"Kanemaki","sequence":"additional","affiliation":[{"name":"National Institute of Genetics, ROIS 5 Department of Chromosome Science , , Mishima, Shizuoka 411-8540 ,","place":["Japan"]},{"name":"Graduate Institute for Advanced Studies, SOKENDAI 6 , Mishima, Shizuoka 411-8540 ,","place":["Japan"]},{"name":"The University of Tokyo 7 Department of Biological Science , , Tokyo 113-0033 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5474-7845","authenticated-orcid":false,"given":"Andrew D.","family":"Stephens","sequence":"additional","affiliation":[{"name":"University of Massachusetts Amherst 8 Biology Department , , Amherst, MA 01003"},{"name":"University of Massachusetts Amherst 9 Molecular and Cellular Biology , , Amherst, MA 01003 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1981-1818","authenticated-orcid":false,"given":"Vadim","family":"Backman","sequence":"additional","affiliation":[{"name":"Northwestern University 1 Department of Biomedical Engineering , , Evanston, IL 60208 ,","place":["USA"]},{"name":"Center for Physical Genomics and Engineering, Northwestern University 3 , Evanston, IL 60208 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"237","published-online":{"date-parts":[[2025,2,11]]},"reference":[{"key":"2025021214014138000_JCS262161C1","doi-asserted-by":"publisher","first-page":"E6372","DOI":"10.1073\/pnas.1521269113","article-title":"Label-free imaging of the native, living cellular nanoarchitecture using partial-wave spectroscopic microscopy","volume":"113","author":"Almassalha Luay","year":"2016","journal-title":"Proc. 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