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However, it remains unknown whether heterogeneity in phosphorylation of key structural proteins alters tissue integrity and organ function. Here, osteopontin phosphorylation level declined in hypo- and hyper- phosphatemia mouse models exhibiting skeletal deformities. Phosphorylation increased cohesion between osteopontin polymers, and adhesion of osteopontin to hydroxyapatite, enhancing energy dissipation. Fracture toughness, a measure of bone\u2019s mechanical competence, increased with ex-vivo phosphorylation of wildtype mouse bones and declined with ex-vivo dephosphorylation. In osteopontin-deficient mice, global matrix phosphorylation level was not associated with toughness. Our findings suggest that phosphorylated osteopontin promotes fracture toughness in a dose-dependent manner through increased interfacial bond formation. In the absence of osteopontin, phosphorylation increases electrostatic repulsion, and likely protein alignment and interfilament distance leading to decreased fracture resistance. These mechanisms may be of importance in other connective tissues, and the key to unraveling cell\u2013matrix interactions in diseases.<\/jats:p>","DOI":"10.7554\/elife.58184","type":"journal-article","created":{"date-parts":[[2020,12,9]],"date-time":"2020-12-09T08:55:57Z","timestamp":1607504157000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.58184","source":"Crossref","is-referenced-by-count":17,"title":["The role of extracellular matrix phosphorylation on energy dissipation in bone"],"prefix":"10.7554","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9013-2469","authenticated-orcid":true,"given":"Stacyann","family":"Bailey","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Grazyna E","family":"Sroga","sequence":"additional","affiliation":[{"name":"Department 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