{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T12:09:30Z","timestamp":1778328570815,"version":"3.51.4"},"reference-count":78,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T00:00:00Z","timestamp":1772841600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T00:00:00Z","timestamp":1772841600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Protein Science"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Transthyretin (TTR) is a plasma protein that functions as a carrier for thyroxine and retinol binding proteins. On the other hand, TTR is also known as one of the major amyloidogenic proteins, and the deposition of TTR in various organs is associated with the onset of systemic amyloidosis. Nevertheless, it has been difficult to reproduce amyloid fibril formation of TTR under physiological conditions in vitro, because TTR exists as a homotetramer with very high structural stability. However, even when the tetramer dissociation is induced, as has been done at mildly acidic pH, the physical properties of TTR aggregates formed in vitro differ from those of ex vivo TTR fibrils in terms of fibril morphology and seeding effect, highlighting the importance of elucidating the process of TTR amyloid fibril formation under physiological conditions. In this study, we have investigated ultrasonication\u2010induced amyloid fibril formation of TTR under neutral pH in combination with 2,2,2\u2010trifluoroethanol\u2010 or fragmentation\u2010induced conformational destabilization, using thioflavin T fluorescence assay, circular dichroism spectroscopy, and transmission electron microscope observation. When full\u2010length TTR (wild\u2010type, V30M, and L55P) and TTR49\u2010127 were incubated under quiescence, they only formed prefibrillar aggregates. However, we have found that mature amyloid fibrils formed in both full\u2010length TTR and TTR49\u2010127 under ultrasonication. These findings indicate that mechanical stress, as applied here by ultrasonication, is another key factor essential for overcoming the energy barrier to form mature TTR amyloid fibrils at physiological pH.<\/jats:p>","DOI":"10.1002\/pro.70524","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T15:07:45Z","timestamp":1772982465000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Ultrasonication\u2010induced in vitro formation of transthyretin mature amyloid fibrils at neutral\n                    <scp>pH<\/scp>"],"prefix":"10.1002","volume":"35","author":[{"given":"Keisuke","family":"Yuzu","sequence":"first","affiliation":[{"name":"Department of Chemistry, Graduate School of Science Kobe University  Kobe Hyogo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naoki","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Division of Biophysics, 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