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Failure of fibrin clots can result in life\u2010threating complications, such as stroke or pulmonary embolism. The dependence of rupture resistance of fibrin networks (uncracked and cracked) on fibrin(ogen) concentrations in the (patho)physiological 1\u20135\u00a0g\u00a0L<jats:sup>\u22121<\/jats:sup> range is explored by performing the ultrastructural studies and theoretical analysis of the experimental stress\u2013strain profiles available from mechanical tensile loading assays. Fibrin fibers in the uncracked network stretched evenly, whereas, in the cracked network, fibers around the crack tip showed greater deformation. Unlike fibrin fibers in cracked networks formed at the lower 1\u20132.7\u00a0g\u00a0L<jats:sup>\u22121<\/jats:sup> fibrinogen concentrations, fibers formed at the higher 2.7\u20135\u00a0g\u00a0L<jats:sup>\u22121<\/jats:sup> concentrations align and stretch simultaneously. Cracked fibrin networks formed in higher fibrinogen solutions are tougher yet less extensible. Statistical modeling revealed that the characteristic strain for fiber alignment, crack size, and fracture toughness of fibrin networks control their rupture resistance. The results obtained provide a structural and biomechanical basis to quantitatively understand the material properties of blood plasma clots and to illuminate the mechanisms of their rupture.<\/jats:p>","DOI":"10.1002\/adhm.202300096","type":"journal-article","created":{"date-parts":[[2023,8,23]],"date-time":"2023-08-23T15:42:39Z","timestamp":1692805359000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Biomechanics, Energetics, and Structural Basis of Rupture of Fibrin Networks"],"prefix":"10.1002","volume":"12","author":[{"given":"Ranjini K.","family":"Ramanujam","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering, Rutgers The State University of New Jersey  Piscataway NJ 08854 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farkhad","family":"Maksudov","sequence":"additional","affiliation":[{"name":"Department of Chemistry University of Massachusetts  Lowell MA 01854 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rustem I.","family":"Litvinov","sequence":"additional","affiliation":[{"name":"Department of Cell and Developmental Biology University of Pennsylvania Perelman School of Medicine  Philadelphia PA 19104 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chandrasekaran","family":"Nagaswami","sequence":"additional","affiliation":[{"name":"Department of Cell and Developmental Biology University of Pennsylvania Perelman School of Medicine  Philadelphia PA 19104 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John W.","family":"Weisel","sequence":"additional","affiliation":[{"name":"Department of Cell and Developmental Biology University of Pennsylvania Perelman School of Medicine  Philadelphia PA 19104 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1213-4447","authenticated-orcid":false,"given":"Valerie","family":"Tutwiler","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Rutgers The State University of New Jersey  Piscataway NJ 08854 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeri","family":"Barsegov","sequence":"additional","affiliation":[{"name":"Department of Chemistry University of Massachusetts  Lowell MA 01854 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,8,31]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.14450"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1213\/ANE.0b013e31823a088c"},{"key":"e_1_2_9_3_1","first-page":"129","volume":"18","author":"B\u0115lohl\u00e1vek J.","year":"2013","journal-title":"Exp. 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