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The intrinsically disordered proteome is altered in cancer cells compared to normal cells. Nevertheless, how the emergence of these proteins is associated with the intracellular physical environment remains unknown. Here, we investigated intracellular dynamics during tumorigenesis using normal, precancerous, and tumor-derived organoids by elastic incoherent neutron scattering (EINS) and quasi-elastic neutron scattering (QENS). EINS analysis revealed a decrease in atomic mean-square displacement from control to precancerous and tumor organoids. In contrast, QENS analysis demonstrated gradual decreases in both the elastic fraction and correlation time, indicating that a larger fraction of intracellular molecules undergoes faster motions during tumorigenesis. These findings suggest that the intracellular physical state is progressively remodeled during cancer development and provide a physical perspective of tumorigenesis.<\/jats:p>","DOI":"10.1021\/acs.jpclett.6c02647","type":"journal-article","created":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T07:02:15Z","timestamp":1791788535000},"page":"12063-12068","source":"Crossref","is-referenced-by-count":0,"title":["Intracellular\nMolecular Dynamics Progressively Change\nduring Carcinogenesis Revealed by Elastic and Quasi-Elastic Neutron\nScattering"],"prefix":"10.1021","volume":"17","author":[{"given":"Daisuke","family":"Muto","sequence":"first","affiliation":[{"name":"Chiba Cancer Center Research Institute , , ,","place":["Chiba, Japan, 260-8717"]},{"name":"Chiba University , , ,","place":["Chiba, Japan, 260-8670"]},{"name":"Chiba University , , ,","place":["Chiba, Japan, 263-8522"]},{"name":"Chiba University , , ,","place":["Chiba, Japan, 263-8522"]},{"name":"National Institutes for Quantum Science and Technology , , ,","place":["Chiba, Japan, 263-8555"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuhito","family":"Matsuo","sequence":"additional","affiliation":[{"name":"Hiroshima International University , , ,","place":["Hiroshima, Japan, 739-2695"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9630-1630","authenticated-orcid":true,"given":"Tilo","family":"Seydel","sequence":"additional","affiliation":[{"name":"Institut Laue Langevin , ,","place":["Grenoble, France, 38042"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akiko","family":"Endo","sequence":"additional","affiliation":[{"name":"Chiba Cancer Center Research Institute , , ,","place":["Chiba, Japan, 260-8717"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Turbant","sequence":"additional","affiliation":[{"name":"Institut Laue Langevin , ,","place":["Grenoble, France, 38042"]},{"name":"Universite\u0301 Grenoble Alpes, CNRS, LiPhy , ,","place":["Grenoble, France, 38400"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4975-1812","authenticated-orcid":true,"given":"Yoshitaka","family":"Hippo","sequence":"additional","affiliation":[{"name":"Chiba Cancer Center Research Institute , , ,","place":["Chiba, Japan, 260-8717"]},{"name":"Chiba University , , ,","place":["Chiba, Japan, 260-8670"]},{"name":"Chiba Cancer Center Research Institute , , ,","place":["Chiba, Japan, 260-8717"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuke","family":"Suenaga","sequence":"additional","affiliation":[{"name":"Chiba Cancer Center Research Institute , , ,","place":["Chiba, Japan, 260-8717"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5151-7710","authenticated-orcid":true,"given":"Judith","family":"Peters","sequence":"additional","affiliation":[{"name":"Institut Laue Langevin , ,","place":["Grenoble, France, 38042"]},{"name":"Universite\u0301 Grenoble Alpes, CNRS, LiPhy , ,","place":["Grenoble, France, 38400"]},{"name":"Institut Universitaire de France , ,","place":["Paris, France, 75231"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,10,12]]},"reference":[{"key":"2026102208022694500_cit1","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1158\/2159-8290.CD-21-1059","article-title":"Hallmarks\nof Cancer: New Dimensions","volume":"12","author":"Hanahan","year":"2022","journal-title":"Cancer Discov"},{"key":"2026102208022694500_cit2","doi-asserted-by":"publisher","first-page":"1800","DOI":"10.1038\/s41592-024-02564-4","article-title":"Probing\nthe physical hallmarks of\ncancer","volume":"22","author":"Nia","year":"2025","journal-title":"Nat. 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Biophys"},{"key":"2026102208022694500_cit4","doi-asserted-by":"publisher","first-page":"4311","DOI":"10.1039\/D3NA00218G","article-title":"Fluorescent\nnano- and microparticles for sensing cellular\nmicroenvironment: past, present and future applications","volume":"5","author":"Grasso","year":"2023","journal-title":"Nanoscale Adv."},{"issue":"8","key":"2026102208022694500_cit5","doi-asserted-by":"publisher","first-page":"2786","DOI":"10.1021\/acs.bioconjchem.8b00412","article-title":"One-Pot Synthesis\nof Highly Dispersible Fluorescent Nanodiamonds for Bioconjugation","volume":"29","author":"Terada","year":"2018","journal-title":"Bioconjug Chem."},{"key":"2026102208022694500_cit6","doi-asserted-by":"publisher","first-page":"654","DOI":"10.3390\/medicina58050654","article-title":"Water Dynamics\nin Cancer Cells: Lessons\nfrom Quasielastic Neutron Scattering","volume":"58","author":"Martins","year":"2022","journal-title":"Medicina\n(Kaunas)"},{"key":"2026102208022694500_cit7","doi-asserted-by":"publisher","first-page":"8716","DOI":"10.1021\/acs.jpclett.6c01914","article-title":"How Polarization\nSwitch Influences Both Charge Separation and Carrier Recombination\nin Hybrid Perovskites","volume":"17","author":"Hu","year":"2026","journal-title":"J. Phys. Chem. Lett."},{"key":"2026102208022694500_cit8","doi-asserted-by":"publisher","first-page":"21079","DOI":"10.1038\/s41598-023-47649-w","article-title":"Cellular dynamics\nas a marker of normal-to-cancer transition in human cells","volume":"13","author":"Marques","year":"2023","journal-title":"Sci. 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Biotechnol."},{"key":"2026102208022694500_cit15","doi-asserted-by":"publisher","first-page":"530","DOI":"10.1038\/s41576-025-00929-9","article-title":"Emergence and evolution of protein-coding\nde novo genes","volume":"27","author":"Bornberg-Bauer","year":"2026","journal-title":"Nat. Rev. Genet"},{"key":"2026102208022694500_cit16","doi-asserted-by":"publisher","first-page":"1552","DOI":"10.3390\/ijms25031552","article-title":"The Proteomic Analysis of Cancer-Related\nAlterations in the Human Unfoldome","volume":"25","author":"Paromov","year":"2024","journal-title":"Int. J.\nMol. Sci."},{"key":"2026102208022694500_cit17","doi-asserted-by":"publisher","DOI":"10.15252\/embr.202154321","article-title":"Open reading\nframe dominance indicates\nprotein-coding potential of RNAs","volume":"23","author":"Suenaga","year":"2022","journal-title":"EMBO Rep"},{"key":"2026102208022694500_cit18","doi-asserted-by":"publisher","first-page":"1237378","DOI":"10.3389\/fonc.2024.1237378","article-title":"Inhibition of OCT4\nbinding at the\nMYCN locus induces neuroblastoma cell death accompanied by downregulation\nof transcripts with high-open reading frame dominance","volume":"14","author":"Nakatani","year":"2024","journal-title":"Front Oncol"},{"key":"2026102208022694500_cit19","doi-asserted-by":"crossref","unstructured":"Suenaga, Y.; Kogashi, H.; Nakatani, K.; Lin, J.; Hasegawa, Y.; Kugou, K.; Kawashima, Y.; Furukawa, E.; Okumura, K.; Kita, E.; et al.; Global changes in open reading frame\ndominance of RNAs during cancer initiation and progression.  bioRxiv, June 5, 2023.10.1101\/2023.06.02.543339.","DOI":"10.1101\/2023.06.02.543339"},{"key":"2026102208022694500_cit20","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1007\/978-1-4939-3603-8_2","article-title":"Lentivirus-Based Stable Gene Delivery\ninto Intestinal Organoids","volume":"1422","author":"Maru","year":"2016","journal-title":"Methods Mol. Biol."},{"key":"2026102208022694500_cit21","doi-asserted-by":"publisher","first-page":"1142","DOI":"10.1093\/carcin\/bgz024","article-title":"Kras-driven heterotopic tumor development\nfrom hepatobiliary organoids","volume":"40","author":"Ochiai","year":"2019","journal-title":"Carcinogenesis"},{"issue":"1\u20132","key":"2026102208022694500_cit22","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1524\/zpch.2010.6091","article-title":"Recent Backscattering\nInstrument Developments at the ILL and SNS","volume":"224","author":"Frick","year":"2010","journal-title":"Z. Phys. Chem."},{"key":"2026102208022694500_cit23","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1016\/j.nima.2014.07.029","article-title":"Mantid\u2500Data\nanalysis and visualization package\nfor neutron scattering and SR experiments","volume":"764","author":"Arnold","year":"2014","journal-title":"Nucl.\nInstrum Meth A"},{"issue":"3","key":"2026102208022694500_cit24","doi-asserted-by":"publisher","first-page":"986","DOI":"10.1103\/PhysRev.126.986","article-title":"Theory of\nSlow Neutron Scattering\nby Liquids.1","volume":"126","author":"Rahman","year":"1962","journal-title":"Phys. Rev."},{"issue":"23","key":"2026102208022694500_cit25","doi-asserted-by":"publisher","first-page":"234908","DOI":"10.1063\/1.5049938","article-title":"Analysis of elastic incoherent neutron\nscattering data\nbeyond the Gaussian approximation","volume":"149","author":"Zeller","year":"2018","journal-title":"J. Chem.\nPhys."},{"issue":"9","key":"2026102208022694500_cit26","doi-asserted-by":"publisher","first-page":"2157","DOI":"10.1016\/j.bpj.2013.09.039","article-title":"Correlation\nbetween supercoiling and conformational motions of the bacterial flagellar\nfilament","volume":"105","author":"Stadler","year":"2013","journal-title":"Biophys. J."},{"key":"2026102208022694500_cit27","doi-asserted-by":"publisher","first-page":"812096","DOI":"10.3389\/fmolb.2021.812096","article-title":"Molecular Dynamics of Lysozyme Amyloid\nPolymorphs Studied by Incoherent Neutron Scattering","volume":"8","author":"Matsuo","year":"2022","journal-title":"Front Mol. Biosci"},{"key":"2026102208022694500_cit28","volume-title":"Quasielastic\nNeutron Scattering: Principles and Applications in Solid State Chemistry,\nBiology and Materials Science","author":"Be\u0301e","year":"1988"},{"issue":"50","key":"2026102208022694500_cit29","doi-asserted-by":"publisher","first-page":"16852","DOI":"10.1021\/ja807691j","article-title":"Cytoplasmic\nwater and hydration layer\ndynamics in human red blood cells","volume":"130","author":"Stadler","year":"2008","journal-title":"J. Am. Chem.\nSoc."},{"issue":"6","key":"2026102208022694500_cit30","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1038\/embor.2008.50","article-title":"Down to atomic-scale\nintracellular water dynamics","volume":"9","author":"Jasnin","year":"2008","journal-title":"EMBO reports"},{"issue":"6","key":"2026102208022694500_cit31","doi-asserted-by":"publisher","first-page":"1572","DOI":"10.1016\/j.cell.2020.10.017","article-title":"Cellular Control of Viscosity Counters\nChanges in Temperature and Energy Availability","volume":"183","author":"Persson","year":"2020","journal-title":"Cell"},{"key":"2026102208022694500_cit32","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1016\/S0065-3233(08)60232-6","article-title":"Hydration of proteins\nand polypeptides","volume":"28","author":"Kuntz","year":"1974","journal-title":"Adv. Protein Chem."},{"key":"2026102208022694500_cit33","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1021\/ja00887a004","article-title":"Hydration\nof Deoxyribonucleic Acid.\nII. An Infrared Study","volume":"85","author":"Falk","year":"1963","journal-title":"J. Am. Chem. Soc."},{"key":"2026102208022694500_cit34","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1016\/0005-2760(74)90042-3","article-title":"The hydration of\nphospholipids","volume":"337","author":"Jendrasiak","year":"1974","journal-title":"Biochim. Biophys. Acta"},{"key":"2026102208022694500_cit34a","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1021\/bk-1981-0150.ch029","article-title":"Solution Properties\nof Polysaccharides: Hydration and Compressibility","volume-title":"Solution Properties of Polysaccharides","author":"Gekko","year":"1981"},{"issue":"3","key":"2026102208022694500_cit35","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1016\/j.tcb.2019.12.006","article-title":"Relevance and Regulation of Cell Density","volume":"30","author":"Neurohr","year":"2020","journal-title":"Trends\nCell Biol."},{"key":"2026102208022694500_cit36","doi-asserted-by":"publisher","first-page":"4740","DOI":"10.1039\/b005319h","article-title":"Temperature-dependent\nself-diffusion\ncoefficients of water and six selected molecular liquids for calibration\nin accurate 1H NMR PFG measurements","volume":"2","author":"Holz","year":"2000","journal-title":"Phys. Chem.\nChem. Phys."},{"issue":"3","key":"2026102208022694500_cit37","doi-asserted-by":"publisher","first-page":"1913","DOI":"10.1103\/PhysRevA.31.1913","article-title":"Experimental-Determination\nof the Nature of Diffusive Motions of Water-Molecules at Low-Temperatures","volume":"31","author":"Teixeira","year":"1985","journal-title":"Phys. Rev. A"},{"key":"2026102208022694500_cit38","doi-asserted-by":"publisher","first-page":"02005","DOI":"10.1051\/epjconf\/20158302005","article-title":"High-resolution neutron\nspectroscopy on protein solution\nsamples","volume":"83","author":"Grimaldo","year":"2015","journal-title":"EPJ. Web of Conferences"},{"key":"2026102208022694500_cit39","doi-asserted-by":"crossref","DOI":"10.1007\/978-1-4613-8122-8","volume-title":"Simultaneous Statistical\nInference","author":"Miller","year":"1981"},{"key":"2026102208022694500_cit40","doi-asserted-by":"publisher","first-page":"3924","DOI":"10.1016\/S0006-3495(03)75120-0","article-title":"A measure\nof conformational entropy change during thermal protein unfolding\nusing neutron spectroscopy","volume":"84","author":"Fitter","year":"2003","journal-title":"Biophys. J."},{"key":"2026102208022694500_cit41","doi-asserted-by":"publisher","first-page":"16047","DOI":"10.1073\/pnas.212637899","article-title":"Slaving: solvent\nfluctuations dominate protein dynamics and functions","volume":"99","author":"Fenimore","year":"2002","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"2026102208022694500_cit42","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1038\/nrd4505","article-title":"Targeting the translation machinery\nin cancer","volume":"14","author":"Bhat","year":"2015","journal-title":"Nat. Rev. Drug Discov"},{"key":"2026102208022694500_cit42a","doi-asserted-by":"publisher","first-page":"250","DOI":"10.1158\/0008-5472.CAN-14-2789","article-title":"Targeting\nthe eIF4F translation initiation complex: a critical nexus for cancer\ndevelopment","volume":"75","author":"Pelletier","year":"2015","journal-title":"Cancer Res."}],"container-title":["The Journal of Physical\nChemistry Letters"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acs.jpclett.6c02647","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/jpclcd\/article-pdf\/doi\/10.1021\/acs.jpclett.6c02647\/68814420\/acs.jpclett.6c02647.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/jpclcd\/article-pdf\/doi\/10.1021\/acs.jpclett.6c02647\/68814420\/acs.jpclett.6c02647.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T12:10:13Z","timestamp":1792671013000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/jpclcd\/article\/17\/42\/12063\/5448685\/Intracellular-Molecular-Dynamics-Progressively"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,12]]},"references-count":44,"journal-issue":{"issue":"42","published-online":{"date-parts":[[2026,10,12]]},"published-print":{"date-parts":[[2026,10,22]]}},"URL":"https:\/\/doi.org\/10.1021\/acs.jpclett.6c02647","relation":{},"ISSN":["1948-7185"],"issn-type":[{"value":"1948-7185","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,12]]}}}