{"record":{"author":{"account_ref":null,"orcid":null},"builds_on":[],"content_schema":"pubphys.content.revision/1","content_sha256":"57ef53c9a91bf694cb571cac291515e61e9fda6499f70f3c0b297fc0ad0f6be7","created":"2026-10-03T07:17:57Z","files":[],"origin":{"assisted_by":[],"kind":"seed"},"parents":["5475cf5dc5b1a72283d26dc95dc6e00d7ea4e00096a7c6492e409a1816eeb011"],"salt":"018aed048cd333457f521302af90a84a4a5531d96eae7adca3bd62970e7a0048","schema":"pubphys.record/2","site":"pubphys.com","target":null,"type":"revision"},"content":{"answer_type":"mechanism","assisted_by":[],"external_id":"bio.protein-folding.amyloid-nucleation","kind":"well-posed","literature_status":"open","n":"1","parents":[],"plain":"Some proteins stack into long fibers called amyloids, and the surface of an existing fiber speeds up the birth of new ones, which drives the self-amplifying aggregation seen in neurodegenerative disease. How the fiber surface does this, molecule by molecule, is unknown.","posed_since":"2013","precise":"For A-beta42 at neutral pH and $\\alpha$-synuclein at mildly acidic pH (about 5 to 6) in vitro, aggregation kinetics fit a master equation in which secondary nucleation on fibril surfaces, at rate $k_{2}$ m^$n_{2}$ M (m = monomer concentration, M = fibril mass concentration), dominates the formation of new aggregates. Determine the microscopic steps (adsorption, conformational conversion on the surface, detachment) and compute k_2 and the reaction order n_2 from a molecular model, matching measured values within a factor of 3.","problem_ref":null,"references":"","settled_by":"A molecular simulation or structural-kinetic model that predicts $k_{2}$ and $n_{2}$ and their dependence on sequence mutations, confirmed by bulk kinetics and single-fibril imaging.","status_note":"Kinetic analysis established secondary nucleation as the dominant source of new A-beta42 aggregates in 2013; its molecular steps remain unresolved.","title":"Molecular mechanism of secondary nucleation on amyloid fibrils","topic_ref":"d70805bb63f25bf8902aa9ee3d70d8c036572d9638addfbea7d1b841f5ab7b17"},"attested":{"attestation":{"batch":null,"client_id":null,"id_token_sha256":null,"kind":"platform"},"record_hash":"af6cb084a5ea68e61c06cca518806c6355e88e46df12158859b365fd3b000d37","schema":"pubphys.attested/1"},"envelope":{"attested_hash":"9f3000fe9d54a3aa1b1504051929aba1ecf3e7228f6a44fef09c2eba46e6807a","platform_signature":{"key_id":"c6afc19b31429869751f06879c75cd64ea92654423d15b44be775bf1310a60da","sig":"nhHz_v-UVczVXaDq4tX1SzMVx9f45sHZHYBDIjS0wwcWNDRHgVs2jjb4WyOlpR2zetFl1Iyhsre-lrsF09dCDA"},"schema":"pubphys.envelope/1"},"record_hash":"af6cb084a5ea68e61c06cca518806c6355e88e46df12158859b365fd3b000d37","leaf_index":828}