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Changes in the BCU have been linked to osteoarthritis (OA) progression. Here we report existence of a physiological internal strain gradient (pre-strain) across the BCU at the ultrastructural scale of the extracellular matrix (ECM) constituents, specifically the collagen fibril. We use X-ray scattering that probes changes in the axial periodicity of fibril-level D-stagger of tropocollagen molecules in the matrix fibrils, as a measure of microscopic pre-strain. We find that mineralized collagen nanofibrils in the calcified plate are in tensile pre-strain relative to the underlying trabecular bone. This behaviour contrasts with the previously accepted notion that fibrillar pre-strain (or D-stagger) in collagenous tissues always reduces with mineralization, via reduced hydration and associated swelling pressure. Within the calcified part of the BCU, a finer-scale gradient in pre-strain (0.6% increase over ~50\u03bcm) is observed. The increased fibrillar pre-strain is linked to prior research reporting large tissue-level residual strains under compression. The findings may have biomechanical adaptative significance: higher in-built molecular level resilience\/damage resistance to physiological compression, and disruption of the molecular-level pre-strains during remodelling of the bone-cartilage interface may be potential factors in osteoarthritis-based degeneration.<\/jats:p>","DOI":"10.1371\/journal.pone.0273832","type":"journal-article","created":{"date-parts":[[2022,9,15]],"date-time":"2022-09-15T16:13:06Z","timestamp":1663258386000},"page":"e0273832","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":12,"title":["Collagen pre-strain discontinuity at the bone\u2014Cartilage interface"],"prefix":"10.1371","volume":"17","author":[{"given":"Waqas","family":"Badar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3059-1262","authenticated-orcid":true,"given":"Husna","family":"Ali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivia N.","family":"Brooker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elis","family":"Newham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim","family":"Snow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8783-1282","authenticated-orcid":true,"given":"Nicholas J.","family":"Terrill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianluca","family":"Tozzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Fratzl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin M.","family":"Knight","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2201-8933","authenticated-orcid":true,"given":"Himadri S.","family":"Gupta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,9,15]]},"reference":[{"key":"pone.0273832.ref001","article-title":"Changes in the osteochondral unit during osteoarthritis: Structure, function and cartilage bone crosstalk","author":"SR Goldring","year":"2016","journal-title":"Nature Reviews Rheumatology"},{"key":"pone.0273832.ref002","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1016\/j.joca.2014.05.023","article-title":"Bone-cartilage interface crosstalk in osteoarthritis: Potential pathways and future therapeutic strategies","author":"XL Yuan","year":"2014","journal-title":"Osteoarthritis and Cartilage"},{"key":"pone.0273832.ref003","doi-asserted-by":"crossref","DOI":"10.1016\/S0140-6736(18)32279-7","article-title":"Global, regional, and national incidence, prevalence, and years lived with disability for 354 Diseases and Injuries for 195 countries and territories, 1990\u20132017: A systematic analysis for the Global Burden of Disease Study 2017.","volume":"392","author":"SL James","year":"2018","journal-title":"Lancet"},{"key":"pone.0273832.ref004","first-page":"29","article-title":"Global, regional prevalence, incidence and risk factors of knee osteoarthritis in population-based studies","author":"A Cui","year":"2020","journal-title":"EClinicalMedicine"},{"key":"pone.0273832.ref005","doi-asserted-by":"crossref","first-page":"513","DOI":"10.3109\/1354750X.2016.1140930","article-title":"Biomarkers of (osteo)arthritis","author":"A Mobasheri","year":"2015","journal-title":"Biomarkers"},{"key":"pone.0273832.ref006","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1016\/j.pmatsci.2017.04.013","article-title":"Functional gradients and heterogeneities in biological materials: Design principles, functions, and bioinspired applications","volume":"88","author":"Z Liu","year":"2017","journal-title":"Prog Mater Sci"},{"key":"pone.0273832.ref007","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1007\/BF00583443","article-title":"Form und Bau der Gelenkknorpel in ihren Beziehungen zur Funktion.","volume":"2","author":"A. 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