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Targeted disruption of cell\u2013cell junctions leads to multiple pathological conditions, among them the life\u2010threatening autoimmune blistering disease pemphigus vulgaris (PV). The dissociation of cell\u2013cell junctions by autoantibodies is the hallmark of PV, however, the detailed mechanisms that result in tissue destruction remain unclear. Thus far, research and therapy in PV have focused primarily on immune mechanisms upstream of autoantibody binding, while the biophysical aspects of the cell\u2013cell dissociation process leading to acantholysis are less well studied. In work aimed at illuminating the cellular consequences of autoantibody attachment, it is reported that externally applied mechanical stress mitigates antibody\u2010induced monolayer fragmentation and inhibits p38 MAPK phosphorylation activated by anti\u2010Dsg3 antibody. Further, it is demonstrated that mechanical stress applied externally to cell monolayers enhances cell contractility via RhoA activation and promotes the strengthening of cortical actin, which ultimately mitigates antibody\u2010induced cell\u2013cell dissociation. The study elevates understanding of the mechanism of acantholysis in PV and shifts the paradigm of PV disease development from a focus solely on immune pathways to highlight the key role of physical transformations at the target cell.<\/jats:p>","DOI":"10.1002\/adbi.202000159","type":"journal-article","created":{"date-parts":[[2021,1,4]],"date-time":"2021-01-04T04:51:56Z","timestamp":1609735916000},"source":"Crossref","is-referenced-by-count":13,"title":["Modulation of Mechanical Stress Mitigates Anti\u2010Dsg3 Antibody\u2010Induced Dissociation of Cell\u2013Cell Adhesion"],"prefix":"10.1002","volume":"5","author":[{"given":"Xiaowei","family":"Jin","sequence":"first","affiliation":[{"name":"Department of Mechanical and Materials Engineering University of Nebraska\u2010Lincoln  Lincoln NE 68588 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordan","family":"Rosenbohm","sequence":"additional","affiliation":[{"name":"Department of Mechanical and Materials Engineering University of Nebraska\u2010Lincoln  Lincoln NE 68588 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eunju","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Mechanical and Materials Engineering University of Nebraska\u2010Lincoln  Lincoln NE 68588 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amir Monemian","family":"Esfahani","sequence":"additional","affiliation":[{"name":"Department of Mechanical and Materials Engineering University of Nebraska\u2010Lincoln  Lincoln NE 68588 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina","family":"Seiffert\u2010Sinha","sequence":"additional","affiliation":[{"name":"Department of Dermatology University at Buffalo  Buffalo NY 14203 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"III","given":"James K.","family":"Wahl","sequence":"additional","affiliation":[{"name":"Department of Oral Biology University of Nebraska Medical Center  Lincoln NE 68583 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jung Yul","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Mechanical and Materials Engineering University of Nebraska\u2010Lincoln  Lincoln NE 68588 USA"},{"name":"Mary and Dick Holland Regenerative Medicine Program University of Nebraska Medical Center  Omaha NE 68198 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Animesh A.","family":"Sinha","sequence":"additional","affiliation":[{"name":"Department of Dermatology University at Buffalo  Buffalo NY 14203 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1361-4277","authenticated-orcid":false,"given":"Ruiguo","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Mechanical and Materials Engineering University of Nebraska\u2010Lincoln  Lincoln NE 68588 USA"},{"name":"Mary and Dick Holland Regenerative Medicine Program University of Nebraska Medical Center  Omaha NE 68198 USA"},{"name":"Nebraska Center for Integrated Biomolecular Communication University of Nebraska\u2010Lincoln  Lincoln NE 68588 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,1,4]]},"reference":[{"key":"e_1_2_7_1_1","first-page":"3, 17026","author":"Kasperkiewicz M.","year":"2017","journal-title":"Nat. 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