{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T22:18:21Z","timestamp":1792189101426,"version":"4.4.0"},"reference-count":41,"publisher":"National Academy of Sciences","issue":"52","license":[{"start":{"date-parts":[[2022,12,19]],"date-time":"2022-12-19T00:00:00Z","timestamp":1671408000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["R01DE025702-01"],"award-info":[{"award-number":["R01DE025702-01"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["F31DE026952"],"award-info":[{"award-number":["F31DE026952"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["DGE-1842165"],"award-info":[{"award-number":["DGE-1842165"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2022,12,27]]},"abstract":"<jats:p>\n                    The outstanding mechanical and chemical properties of dental enamel emerge from its complex hierarchical architecture. An accurate, detailed multiscale model of the structure and composition of enamel is important for understanding lesion formation in tooth decay (dental caries), enamel development (amelogenesis) and associated pathologies (e.g., amelogenesis imperfecta or molar hypomineralization), and minimally invasive dentistry. Although features at length scales smaller than 100 nm (individual crystallites) and greater than 50 \u00b5m (multiple rods) are well understood, competing field of view and sampling considerations have hindered exploration of mesoscale features, i.e., at the level of single enamel rods and the interrod enamel (1 to 10 \u00b5m). Here, we combine synchrotron X-ray diffraction at submicrometer resolution, analysis of crystallite orientation distribution, and unsupervised machine learning to show that crystallographic parameters differ between rod head and rod tail\/interrod enamel. This variation strongly suggests that crystallites in different microarchitectural domains also differ in their composition. Thus, we use a dilute linear model to predict the concentrations of minority ions in hydroxylapatite (Mg\n                    <jats:sup>2+<\/jats:sup>\n                    and CO\n                    <jats:sub>3<\/jats:sub>\n                    <jats:sup>2\u2212<\/jats:sup>\n                    \/Na\n                    <jats:sup>+<\/jats:sup>\n                    ) that plausibly explain the observed lattice parameter variations. While differences within samples are highly significant and of similar magnitude, absolute values and the sign of the effect for some crystallographic parameters show interindividual variation that warrants further investigation. By revealing additional complexity at the rod\/interrod level of human enamel and leaving open the possibility of modulation across larger length scales, these results inform future investigations into mechanisms governing amelogenesis and introduce another feature to consider when modeling the mechanical and chemical performance of enamel.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2211285119","type":"journal-article","created":{"date-parts":[[2022,12,19]],"date-time":"2022-12-19T15:09:05Z","timestamp":1671462545000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":39,"title":["Mesoscale structural gradients in human tooth enamel"],"prefix":"10.1073","volume":"119","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5674-9737","authenticated-orcid":false,"given":"Robert","family":"Free","sequence":"first","affiliation":[{"name":"Department of Materials Science and Engineering, Northwestern University, Evanston, IL 60208"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"DeRocher","sequence":"additional","affiliation":[{"name":"Department of Materials Science and Engineering, Northwestern University, Evanston, IL 60208"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0674-4775","authenticated-orcid":false,"given":"Victoria","family":"Cooley","sequence":"additional","affiliation":[{"name":"Department of Materials Science and Engineering, Northwestern University, Evanston, IL 60208"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruqing","family":"Xu","sequence":"additional","affiliation":[{"name":"Argonne National Lab, Advanced Photon Source, Lemont, IL 60439"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8886-4035","authenticated-orcid":false,"given":"Stuart R.","family":"Stock","sequence":"additional","affiliation":[{"name":"Department of Cell and Developmental Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611"},{"name":"Northwestern University, Simpson Querrey Institute, Chicago, IL 60611"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9663-3309","authenticated-orcid":false,"given":"Derk","family":"Joester","sequence":"additional","affiliation":[{"name":"Department of Materials Science and Engineering, Northwestern University, Evanston, IL 60208"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2022,12,19]]},"reference":[{"key":"e_1_3_4_1_2","volume-title":"Ten Cate\u2019s Oral Histology: Development, Structure, and Function","author":"Nanci A.","year":"2012","unstructured":"A. Nanci, Ten Cate\u2019s Oral Histology: Development, Structure, and Function (C.V. Mosby Co., ed. 8, 2012).","edition":"8"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1177\/00220345790580023701"},{"key":"e_1_3_4_3_2","doi-asserted-by":"crossref","unstructured":"K. DeRocher Chemical gradients in human enamel crystallites. Nature 583 66\u201371 (2020) 10.1038\/s41586-020-2433-3.","DOI":"10.1038\/s41586-020-2433-3"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1258950"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2015.00057"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/0003-9969(65)90131-7"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-12185-7"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/0003-9969(61)90110-8"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0185(199803)250:3<268::AID-AR2>3.0.CO;2-X"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF02405364"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/jmicro\/52.6.605"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.2138\/am-1999-0919"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-32425-y"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.archoralbio.2013.08.012"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1111\/jmi.12053"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1017\/S0885715620000251"},{"key":"e_1_3_4_17_2","volume-title":"Department of Materials Science and Engineering","author":"Free R.","year":"2020","unstructured":"R. Free, \u201cThe hierarchical structure of carious tooth enamel in\u00a0vivo rodent models and novel X-ray microdiffraction approaches\u201d in Department of Materials Science and Engineering (Northwestern University, Evanston, Illinois, 2020)."},{"key":"e_1_3_4_18_2","unstructured":"D. Arthur S. Vassilvitskii \u201cK-means++: The advantages of careful seeding\u201d in SODA \u201907: Proceedings of the Eighteenth Annual ACM-SIAM Symposium on Discrete Algorithms (Society for Industrial and Applied Mathematics 3600 University City Science Center Philadelphia PA 2007) pp. 1027\u20131035."},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.3390\/nano10091627"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1107\/S090904950801755X"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1177\/0309324711405761"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-642-68574-3_6"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1177\/10454411000110040601"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1515\/9781501509636-014"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.18689\/mjdl-1000120"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsb.2006.03.008"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmat1263"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2015.10.031"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemmater.6b00811"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2017.02.029"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.2138\/am-2018-6608"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1002\/ar.1092000402"},{"key":"e_1_3_4_33_2","doi-asserted-by":"crossref","unstructured":"A. Boyde \u201cEnamel\u201d in Teeth B. K. B. Berkovitz Eds. (Springer Berlin Heidelberg Berlin Heidelberg 1989) pp. 309\u2013473 10.1007\/978-3-642-83496-7_6.","DOI":"10.1007\/978-3-642-83496-7_6"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5320(78)90053-9"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mtla.2020.100935"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2089"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1080\/08957959608201408"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0021889887087090"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0021889878012844"},{"key":"e_1_3_4_40_2","unstructured":"R. Free D. Joester Human Enamel Mesoscale Variation. (Github 2022) https:\/\/github.com\/bbimatgroup\/human_enamel_mesoscale_variation\/ 2 November 2022."},{"key":"e_1_3_4_41_2","unstructured":"R. Free D. Joester bbimat-group\/human_enamel_mesoscale_variation: Initial Release. (Zenodo 2022) https:\/\/zenodo.org\/record\/7275446#.Y4fV7cvMIuU 2 November 2022."}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2211285119","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,21]],"date-time":"2023-09-21T08:31:38Z","timestamp":1695285098000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/10.1073\/pnas.2211285119"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,19]]},"references-count":41,"journal-issue":{"issue":"52","published-print":{"date-parts":[[2022,12,27]]}},"alternative-id":["10.1073\/pnas.2211285119"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2211285119","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,19]]},"assertion":[{"value":"2022-06-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-10-30","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-12-19","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2211285119"}}