{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T13:00:23Z","timestamp":1790600423323,"version":"4.1.0"},"reference-count":47,"publisher":"American Chemical Society (ACS)","issue":"9","license":[{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000781","name":"European Research Council","doi-asserted-by":"publisher","award":["101228762"],"award-info":[{"award-number":["101228762"]}],"id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002428","name":"Austrian Science Fund","doi-asserted-by":"publisher","award":["10.55776\/PAT2131925"],"award-info":[{"award-number":["10.55776\/PAT2131925"]}],"id":[{"id":"10.13039\/501100002428","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002428","name":"Austrian Science Fund","doi-asserted-by":"publisher","award":["I5771-N"],"award-info":[{"award-number":["I5771-N"]}],"id":[{"id":"10.13039\/501100002428","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Peptide-guided biomineralization is a key process involved in the formation of calcium phosphate (CaP) in bone, yet the peptide\u2013ion encounter complexes at the onset of this process have remained structurally invisible: methods with sufficient resolution to decipher these intermediates would already have lost them to precipitation. Here, we resolve how a mineralization peptide adapts its conformation to recruit inorganic ions during the earliest stages of CaP formation. Using a peptide derived from the calcium-binding domain of secreted phosphoprotein 1 (SPP1), a key regulator of bone formation, we find that Ca2+ association reorganizes the conformational ensemble toward states with increased solvent exposure of Ca2+-coated Asp-rich stretches. These polyionic microenvironments subsequently exhibit spectral perturbations upon phosphate recruitment, consistent with the formation of encounter complexes during the onset of CaP nucleation at the peptide\u2013solvent interface. Access to these transient states is enabled by NMR sensitized with hyperpolarized water (HyperW), which provides a two-order-of-magnitude sensitivity gain and reduces multidimensional acquisition times from hours to seconds\u2500fast enough to capture peptide\u2013ion assemblies immediately after encounter and before precipitation. Together, these results reveal a stepwise mechanism by which an intrinsically disordered mineralization peptide senses and organizes calcium and phosphate ions at the onset of biomineralization.<\/jats:p>","DOI":"10.1021\/jacsau.6c01076","type":"journal-article","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T08:01:55Z","timestamp":1789545715000},"page":"5401-5409","source":"Crossref","is-referenced-by-count":0,"title":["Following Transient\nConformational Adaptations during\nPeptide-Guided Calcium Phosphate Biomineralization with Hyperpolarized\nNMR"],"prefix":"10.1021","volume":"6","author":[{"given":"Fanny","family":"Kormout","sequence":"first","affiliation":[{"name":"University of Vienna , , Wa\u0308hringer Str. 38 , ,","place":["Vienna, Austria, 1090"]},{"name":"University of Vienna , , Wa\u0308hringer Str. 38 , ,","place":["Vienna, Austria, 1090"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ertan","family":"Turhan","sequence":"additional","affiliation":[{"name":"University of Vienna , , Wa\u0308hringer Str. 38 , ,","place":["Vienna, Austria, 1090"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehdi","family":"Soussi-Therond","sequence":"additional","affiliation":[{"name":"University of Vienna , , Wa\u0308hringer Str. 38 , ,","place":["Vienna, Austria, 1090"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milan","family":"Zachrdla","sequence":"additional","affiliation":[{"name":"University of Vienna , , Wa\u0308hringer Str. 38 , ,","place":["Vienna, Austria, 1090"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6455-2136","authenticated-orcid":true,"given":"Dennis","family":"Kurzbach","sequence":"additional","affiliation":[{"name":"University of Vienna , , Wa\u0308hringer Str. 38 , ,","place":["Vienna, Austria, 1090"]},{"name":"University of Vienna , , Wa\u0308hringer Str. 38 , ,","place":["Vienna, Austria, 1090"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,16]]},"reference":[{"issue":"4","key":"2026092808084676200_cit1","doi-asserted-by":"publisher","first-page":"980","DOI":"10.1002\/chem.200500980","article-title":"Mollusk shell formation:\na source of new concepts for understanding biomineralization processes","volume":"12","author":"Addadi","year":"2006","journal-title":"Chemistry"},{"key":"2026092808084676200_cit2","doi-asserted-by":"publisher","first-page":"314","DOI":"10.3389\/fmicb.2013.00314","article-title":"Biomineralization of calcium carbonates\nand their engineered applications: a review","volume":"4","author":"Dhami","year":"2013","journal-title":"Front. Microbiol"},{"issue":"14","key":"2026092808084676200_cit3","doi-asserted-by":"publisher","first-page":"1605903","DOI":"10.1002\/adma.201605903","article-title":"Biomineralization:\nFrom Material Tactics to Biological Strategy","volume":"29","author":"Yao","year":"2017","journal-title":"Adv. Mater."},{"issue":"1","key":"2026092808084676200_cit4","doi-asserted-by":"publisher","first-page":"107665","DOI":"10.1016\/j.jsb.2020.107665","article-title":"Protein-driven biomineralization:\nComparing silica formation in grass silica cells to other biomineralization\nprocesses","volume":"213","author":"Kumar","year":"2021","journal-title":"J. Struct Biol."},{"issue":"2","key":"2026092808084676200_cit5","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1038\/nbt931","article-title":"Enzyme immobilization\nin a biomimetic silica support","volume":"22","author":"Luckarift","year":"2004","journal-title":"Nat. Biotechnol."},{"issue":"11","key":"2026092808084676200_cit6","doi-asserted-by":"publisher","first-page":"4742","DOI":"10.1021\/cr800427g","article-title":"Calcium\nphosphate-based osteoinductive materials","volume":"108","author":"LeGeros","year":"2008","journal-title":"Chem.\nRev."},{"key":"2026092808084676200_cit7","doi-asserted-by":"publisher","first-page":"1507","DOI":"10.1038\/ncomms2490","article-title":"Ion-association complexes unite classical and non-classical\ntheories for the biomimetic nucleation of calcium phosphate","volume":"4","author":"Habraken","year":"2013","journal-title":"Nat. Commun."},{"issue":"28","key":"2026092808084676200_cit8","doi-asserted-by":"publisher","first-page":"12038","DOI":"10.1039\/C5NR01407G","article-title":"Bio-inspired synthesis\nof hybrid silica nanoparticles templated from elastin-like polypeptide\nmicelles","volume":"7","author":"Han","year":"2015","journal-title":"Nanoscale"},{"issue":"1","key":"2026092808084676200_cit9","doi-asserted-by":"publisher","first-page":"121","DOI":"10.3390\/pharmaceutics15010121","article-title":"A Biomimetic,\nSilaffin R5-Based Antigen Delivery Platform","volume":"15","author":"Reichinger","year":"2022","journal-title":"Pharmaceutics"},{"issue":"11","key":"2026092808084676200_cit10","doi-asserted-by":"publisher","first-page":"939","DOI":"10.3928\/0147-7447-20071101-06","article-title":"Calcium phosphates as bone graft\nextenders","volume":"30","author":"Burger","year":"2007","journal-title":"Orthopedics"},{"issue":"12","key":"2026092808084676200_cit11","doi-asserted-by":"publisher","first-page":"1081","DOI":"10.1038\/nmat3822","article-title":"Bone mineralization:\nWater brings order","volume":"12","author":"Duer","year":"2013","journal-title":"Nat.\nMater."},{"issue":"4","key":"2026092808084676200_cit12","doi-asserted-by":"publisher","first-page":"224","DOI":"10.1016\/j.bioactmat.2017.05.007","article-title":"Bone grafts and biomaterials substitutes for bone defect\nrepair: A review","volume":"2","author":"Wang","year":"2017","journal-title":"Bioact. Mater."},{"key":"2026092808084676200_cit13","doi-asserted-by":"publisher","first-page":"8456","DOI":"10.1038\/s41598-019-44620-6","article-title":"Bone mineral: New insights into its\nchemical composition","volume":"9","author":"Von Euw","year":"2019","journal-title":"Sci. Rep."},{"key":"2026092808084676200_cit14","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/978-1-4614-0659-4_1","article-title":"Fuzzy complexes: a more stochastic\nview of protein function","volume":"725","author":"Fuxreiter","year":"2012","journal-title":"Adv. Exp. Med. Biol."},{"issue":"2","key":"2026092808084676200_cit15","doi-asserted-by":"publisher","first-page":"406","DOI":"10.1038\/s41596-023-00921-9","article-title":"Optimal (13)C NMR investigation of\nintrinsically disordered proteins at 1.2 GHz","volume":"19","author":"Schiavina","year":"2024","journal-title":"Nat. Protoc."},{"issue":"3","key":"2026092808084676200_cit16","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1038\/s41580-023-00673-0","article-title":"The molecular basis for cellular\nfunction of intrinsically\ndisordered protein regions","volume":"25","author":"Holehouse","year":"2024","journal-title":"Nat. Rev. Mol. Cell\nBiol."},{"issue":"4","key":"2026092808084676200_cit17","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1016\/j.cellsig.2010.10.003","article-title":"Bone morphogenetic proteins: a critical\nreview","volume":"23","author":"Bragdon","year":"2011","journal-title":"Cell. 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Rev."},{"key":"2026092808084676200_cit20","unstructured":"Bongio, M.; Van den Beucken, J.; Nejadnik, M.; Leeuwenburgh, S.; Kinard, L.; Kasper, F.; Mikos, A.; Jansen, J., Biomimetic modification of\nsynthetic hydrogels by incorporation of adhesive peptides and calcium\nphosphate nanoparticles: in vitro evaluation of cell behavior,2011."},{"issue":"11","key":"2026092808084676200_cit21","doi-asserted-by":"publisher","first-page":"1217","DOI":"10.1016\/j.dental.2017.07.015","article-title":"Rapid biomimetic remineralization\nof the demineralized enamel surface using nano-particles of amorphous\ncalcium phosphate guided by chimaeric peptides","volume":"33","author":"Xiao","year":"2017","journal-title":"Dental Mater."},{"issue":"1","key":"2026092808084676200_cit22","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1186\/s40510-018-0216-2","article-title":"Role of osteopontin\nin bone remodeling and orthodontic tooth movement: a review","volume":"19","author":"Singh","year":"2018","journal-title":"Prog. 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Mater."},{"issue":"1","key":"2026092808084676200_cit28","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1038\/s42004-020-0301-6","article-title":"Hyperpolarized\nwater\nthrough dissolution dynamic nuclear polarization with UV-generated\nradicals","volume":"3","author":"Pinon","year":"2020","journal-title":"Commun. Chem."},{"issue":"20","key":"2026092808084676200_cit29","doi-asserted-by":"publisher","first-page":"9267","DOI":"10.1021\/jacs.0c00807","article-title":"Assessing Site-Specific Enhancements\nImparted by Hyperpolarized\nWater in Folded and Unfolded Proteins by 2D HMQC NMR","volume":"142","author":"Szekely","year":"2020","journal-title":"J. Am. Chem. Soc."},{"issue":"7","key":"2026092808084676200_cit30","doi-asserted-by":"publisher","first-page":"1621","DOI":"10.1038\/s41596-022-00693-8","article-title":"Hyperpolarized\nwater as universal\nsensitivity booster in biomolecular NMR","volume":"17","author":"Hilty","year":"2022","journal-title":"Nat.\nProtoc."},{"key":"2026092808084676200_cit31","doi-asserted-by":"publisher","DOI":"10.1002\/chem.202502067","article-title":"Deep Learning for Hyperpolarized\nNMR of Intrinsically\nDisordered Proteins Without Resolution Loss: Access to Short-Lived\nIntermediates","volume":"31","author":"Turhan","year":"2025","journal-title":"Chemistry"},{"issue":"40","key":"2026092808084676200_cit32","doi-asserted-by":"publisher","first-page":"36920","DOI":"10.1021\/jacs.5c15053","article-title":"Residue-Resolved Liquid-State\nHyperpolarized NMR of Peptide Condensate Surfaces","volume":"147","author":"Brandis","year":"2025","journal-title":"J. Am. Chem. Soc."},{"key":"2026092808084676200_cit33","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202523739","article-title":"Residue-Specific\nSignatures of Structural Water Identified by Dissolution Dynamic Nuclear\nPolarization with UV-Generated Radicals","volume":"65","author":"Hecker","year":"2026","journal-title":"Angew.\nChem., Int. Ed."},{"issue":"13","key":"2026092808084676200_cit34","doi-asserted-by":"publisher","first-page":"2300","DOI":"10.1002\/cbic.202100139","article-title":"Binding mode characterization\nof osteopontin on hydroxyapatite by solution NMR spectroscopy","volume":"22","author":"Holzinger","year":"2021","journal-title":"ChemBioChem"},{"issue":"1","key":"2026092808084676200_cit35","doi-asserted-by":"publisher","first-page":"15722","DOI":"10.1038\/s41598-020-72786-x","article-title":"Osteopontin\nregulates biomimetic\ncalcium phosphate crystallization from disordered mineral layers covering\napatite crystallites","volume":"10","author":"Iline-Vul","year":"2020","journal-title":"Sci. Rep"},{"key":"2026092808084676200_cit36","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1016\/j.bone.2014.05.020","article-title":"Osteopontin binds multiple calcium\nions with high affinity\nand independently of phosphorylation status","volume":"66","author":"Kla\u0308ning","year":"2014","journal-title":"Bone"},{"issue":"3","key":"2026092808084676200_cit37","doi-asserted-by":"publisher","first-page":"879","DOI":"10.1096\/fasebj.6.3.1740237","article-title":"Bone structure: from \u00e5ngstroms to microns","volume":"6","author":"Weiner","year":"1992","journal-title":"FASEB J."},{"issue":"4","key":"2026092808084676200_cit38","doi-asserted-by":"publisher","first-page":"912","DOI":"10.1002\/jcb.21558","article-title":"Control of osteopontin\nsignaling\nand function by post-translational phosphorylation and protein folding","volume":"102","author":"Kazanecki","year":"2007","journal-title":"J. Cell. Biochem."},{"issue":"6","key":"2026092808084676200_cit39","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1003106","article-title":"Cooperative\nbinding","volume":"9","author":"Stefan","year":"2013","journal-title":"PLoS Comput.\nBiol."},{"issue":"1","key":"2026092808084676200_cit40","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1002\/anie.201608903","article-title":"Investigation\nof Intrinsically Disordered Proteins through Exchange with Hyperpolarized\nWater","volume":"56","author":"Kurzbach","year":"2017","journal-title":"Angew. Chem., Int. Ed."},{"issue":"27","key":"2026092808084676200_cit41","doi-asserted-by":"publisher","first-page":"6492","DOI":"10.1021\/acs.jpcb.7b03052","article-title":"Modeling of\nPolarization Transfer Kinetics in Protein\nHydration Using Hyperpolarized Water","volume":"121","author":"Kim","year":"2017","journal-title":"J. Phys.\nChem. B"},{"issue":"51","key":"2026092808084676200_cit42","doi-asserted-by":"publisher","first-page":"13418","DOI":"10.1002\/chem.201802885","article-title":"High-Resolution NMR\nof Folded Proteins in Hyperpolarized Physiological Solvents","volume":"24","author":"Kaderavek","year":"2018","journal-title":"Chemistry"},{"issue":"10","key":"2026092808084676200_cit43","doi-asserted-by":"publisher","first-page":"6169","DOI":"10.1021\/acs.analchem.8b00585","article-title":"High-resolution 2D\nNMR of disordered proteins enhanced by hyperpolarized water","volume":"90","author":"Szekely","year":"2018","journal-title":"Anal. Chem."},{"issue":"2\u20133","key":"2026092808084676200_cit44","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1007\/s10858-020-00301-5","article-title":"Sensitivity-enhanced\nthree-dimensional and carbon-detected two-dimensional NMR of proteins\nusing hyperpolarized water","volume":"74","author":"Olsen","year":"2020","journal-title":"J. Biomol. NMR"},{"key":"2026092808084676200_cit45","doi-asserted-by":"publisher","first-page":"20191","DOI":"10.1021\/acs.analchem.5c02945","article-title":"Hyperpolarized\nNMR Combined with Quantum Mechanical Simulations Reveal Atomistic\nStructures of Calcium Phosphate Prenucleation Clusters","volume":"97","author":"Po\u0308tzl","year":"2025","journal-title":"Anal. Chem."},{"issue":"11","key":"2026092808084676200_cit46","doi-asserted-by":"publisher","first-page":"7666","DOI":"10.1021\/acs.analchem.0c00516","article-title":"Assessing the Onset\nof Calcium Phosphate Nucleation\nby Hyperpolarized Real-Time NMR","volume":"92","author":"Weber","year":"2020","journal-title":"Anal. Chem."},{"issue":"1","key":"2026092808084676200_cit47","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1016\/j.jsb.2008.04.008","article-title":"Ultrastructural matrix\u2013mineral\nrelationships in avian eggshell, and effects of osteopontin on calcite\ngrowth in vitro","volume":"163","author":"Chien","year":"2008","journal-title":"J. Struct. Biol."}],"container-title":["JACS Au"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/jacsau.6c01076","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/jaaucr\/article-pdf\/6\/9\/5401\/68526576\/jacsau.6c01076.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/jaaucr\/article-pdf\/6\/9\/5401\/68526576\/jacsau.6c01076.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T12:31:05Z","timestamp":1790598665000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/jaaucr\/article\/6\/9\/5401\/5430956\/Following-Transient-Conformational-Adaptations"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,16]]},"references-count":47,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9,16]]},"published-print":{"date-parts":[[2026,9,28]]}},"URL":"https:\/\/doi.org\/10.1021\/jacsau.6c01076","relation":{},"ISSN":["2691-3704"],"issn-type":[{"value":"2691-3704","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,16]]}}}