{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T20:03:05Z","timestamp":1767902585690,"version":"3.49.0"},"reference-count":70,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,8,5]],"date-time":"2025-08-05T00:00:00Z","timestamp":1754352000000},"content-version":"vor","delay-in-days":4,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100003484","name":"Heinrich-Heine-Universit\u00e4t D\u00fcsseldorf","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003484","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Eur Biophys J"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Multiple myeloma is a blood cancer characterized by plasma cell proliferation and excessive production of monoclonal proteins, often leading to renal complications and other forms of organ damage. A set of nine immunoglobulin free light chain (FLC) samples purified from urine of multiple myeloma patients was subjected to sedimentation velocity analysis. Aim of the study was to track changes of the oligomerization state of each FLC while triggering reduction-induced aggregation into larger structures. Sedimentation velocity experiments, combined with further techniques sensitive to structural changes, were performed to determine the degree of FLC oligomerization in each patient sample under different experimental conditions. Structurally, the FLC monomers are stabilized by two intramolecular disulfide bonds, while covalent dimerization occurs through an unpaired C-terminal cysteine residue. Incubation with the reducing agent TCEP cleaves intra- and intermolecular disulfide bonds, destabilizing both monomers and dimers. Remarkably, different incubation times revealed that destabilized dimers do not dissociate into stable monomers but instead accumulate directly into oligomers and higher-order aggregates. In addition to larger aggregates, fragments with sizes around 1\u00a0S were detected with increasing TCEP incubation time. This fragmentation behavior was consistent among FLCs originating from the immunoglobulin kappa variable 1-33 gene (IGKV1-33). Sedimentation velocity-based characterization of FLCs can provide insights into the relationship between their stability and aggregation capacity. An understanding of this relationship is crucial for the development of therapeutic strategies to prevent renal complications associated with monoclonal gammopathies such as multiple myeloma.<\/jats:p>","DOI":"10.1007\/s00249-025-01788-2","type":"journal-article","created":{"date-parts":[[2025,8,5]],"date-time":"2025-08-05T18:47:14Z","timestamp":1754419634000},"page":"365-383","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Tracking reduction-induced molecular changes in pathological free light chains by SV-AUC"],"prefix":"10.1007","volume":"54","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-5060-2124","authenticated-orcid":false,"given":"Florian T.","family":"Tucholski","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca","family":"Sternke-Hoffmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Pauly","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rasmus K.","family":"Norrild","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amelie","family":"Boquoi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roland","family":"Fenk","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luitgard","family":"Nagel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander K.","family":"Buell","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rainer","family":"Haas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dieter","family":"Willbold","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,8,5]]},"reference":[{"key":"1788_CR1","doi-asserted-by":"publisher","first-page":"961","DOI":"10.1146\/annurev.bi.48.070179.004525","volume":"48","author":"LM Amzel","year":"1979","unstructured":"Amzel LM, Poljak RJ (1979) Three-dimensional structure of immunoglobulins. Annu Rev Biochem 48:961\u2013997. https:\/\/doi.org\/10.1146\/annurev.bi.48.070179.004525","journal-title":"Annu Rev Biochem"},{"key":"1788_CR2","doi-asserted-by":"publisher","first-page":"2328","DOI":"10.1074\/jbc.M116.750323","volume":"292","author":"K Andrich","year":"2017","unstructured":"Andrich K, Hegenbart U, Kimmich C et al (2017) Aggregation of full-length immunoglobulin light chains from systemic light chain amyloidosis (AL) patients is remodeled by epigallocatechin-3-gallate. J Biol Chem 292:2328\u20132344. https:\/\/doi.org\/10.1074\/jbc.M116.750323","journal-title":"J Biol Chem"},{"key":"1788_CR3","doi-asserted-by":"publisher","first-page":"500","DOI":"10.2174\/138920309789351949","volume":"10","author":"E Baden","year":"2009","unstructured":"Baden E, Sikkink L, Ramirez-Alvarado M (2009) Light chain amyloidosis: current findings and future prospects. CPPS 10:500\u2013508. https:\/\/doi.org\/10.2174\/138920309789351949","journal-title":"CPPS"},{"key":"1788_CR4","doi-asserted-by":"publisher","first-page":"1289","DOI":"10.1038\/ki.2011.94","volume":"79","author":"K Basnayake","year":"2011","unstructured":"Basnayake K, Stringer SJ, Hutchison CA, Cockwell P (2011) The biology of immunoglobulin free light chains and kidney injury. Kidney Int 79:1289\u20131301. https:\/\/doi.org\/10.1038\/ki.2011.94","journal-title":"Kidney Int"},{"key":"1788_CR5","doi-asserted-by":"publisher","first-page":"1889","DOI":"10.1001\/archinte.158.17.1889","volume":"158","author":"J Blad\u00e9","year":"1998","unstructured":"Blad\u00e9 J, Fern\u00e1ndez-Llama P, Bosch F et al (1998) Renal failure in multiple myeloma: presenting features and predictors of outcome in 94 patients from a single institution. Arch Intern Med 158:1889. https:\/\/doi.org\/10.1001\/archinte.158.17.1889","journal-title":"Arch Intern Med"},{"key":"1788_CR6","doi-asserted-by":"publisher","first-page":"458","DOI":"10.1007\/s10541-005-0137-9","volume":"70","author":"OP Bliznyukov","year":"2005","unstructured":"Bliznyukov OP, Kozmin LD, Vysotskaya LL et al (2005) Human immunoglobulin light chains \u03bb form amyloid fibrils and granular aggregates in solution. Biochem Mosc 70:458\u2013466. https:\/\/doi.org\/10.1007\/s10541-005-0137-9","journal-title":"Biochem Mosc"},{"key":"1788_CR7","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1006\/jmbi.1994.1582","volume":"242","author":"P Bork","year":"1994","unstructured":"Bork P, Holm L, Sander C (1994) The immunoglobulin fold. J Mol Biol 242:309\u2013320. https:\/\/doi.org\/10.1006\/jmbi.1994.1582","journal-title":"J Mol Biol"},{"key":"1788_CR8","doi-asserted-by":"publisher","first-page":"3208","DOI":"10.1073\/pnas.74.8.3208","volume":"74","author":"S Brahms","year":"1977","unstructured":"Brahms S, Brahms J, Spach G, Brack A (1977) Identification of \u03b2,\u03b2-turns and unordered conformations in polypeptide chains by vacuum ultraviolet circular dichroism. Proc Natl Acad Sci USA 74:3208\u20133212. https:\/\/doi.org\/10.1073\/pnas.74.8.3208","journal-title":"Proc Natl Acad Sci USA"},{"key":"1788_CR9","doi-asserted-by":"crossref","unstructured":"Brautigam CA (2015) Calculations and publication-quality illustrations for analytical ultracentrifugation data. In: Methods in enzymology. Elsevier, pp 109\u2013133","DOI":"10.1016\/bs.mie.2015.05.001"},{"key":"1788_CR10","doi-asserted-by":"publisher","first-page":"2648","DOI":"10.1021\/jo00008a014","volume":"56","author":"JA Burns","year":"1991","unstructured":"Burns JA, Butler JC, Moran J, Whitesides GM (1991) Selective reduction of disulfides by tris(2-carboxyethyl)phosphine. J Org Chem 56:2648\u20132650. https:\/\/doi.org\/10.1021\/jo00008a014","journal-title":"J Org Chem"},{"key":"1788_CR11","doi-asserted-by":"publisher","first-page":"3394","DOI":"10.1016\/S0021-9258(19)69621-3","volume":"256","author":"S Damodaran","year":"1981","unstructured":"Damodaran S, Kinsella JE (1981) The effects of neutral salts on the stability of macromolecules: a new approach using a protein-ligand binding system. J Biol Chem 256:3394\u20133398. https:\/\/doi.org\/10.1016\/S0021-9258(19)69621-3","journal-title":"J Biol Chem"},{"key":"1788_CR12","doi-asserted-by":"publisher","first-page":"232","DOI":"10.3390\/hemato3010019","volume":"3","author":"L Del Pozo-Yauner","year":"2022","unstructured":"Del Pozo-Yauner L, Turbat-Herrera EA, P\u00e9rez-Carre\u00f3n JI, Herrera GA (2022) From the light chain sequence to the tissue microenvironment: contribution of the mesangial cells to glomerular amyloidosis. Hemato 3:232\u2013267. https:\/\/doi.org\/10.3390\/hemato3010019","journal-title":"Hemato"},{"key":"1788_CR13","doi-asserted-by":"publisher","first-page":"7133","DOI":"10.1021\/bi00483a001","volume":"29","author":"KA Dill","year":"1990","unstructured":"Dill KA (1990) Dominant forces in protein folding. Biochemistry 29:7133\u20137155. https:\/\/doi.org\/10.1021\/bi00483a001","journal-title":"Biochemistry"},{"key":"1788_CR14","doi-asserted-by":"publisher","first-page":"10627","DOI":"10.1021\/acs.analchem.1c01955","volume":"93","author":"M Dupr\u00e9","year":"2021","unstructured":"Dupr\u00e9 M, Duchateau M, Sternke-Hoffmann R et al (2021) De novo sequencing of antibody light chain proteoforms from patients with multiple myeloma. Anal Chem 93:10627\u201310634. https:\/\/doi.org\/10.1021\/acs.analchem.1c01955","journal-title":"Anal Chem"},{"key":"1788_CR15","doi-asserted-by":"publisher","first-page":"112983","DOI":"10.1016\/j.colsurfb.2022.112983","volume":"221","author":"V D\u017eupponov\u00e1","year":"2023","unstructured":"D\u017eupponov\u00e1 V, \u017dold\u00e1k G (2023) Aggregation mechanism and branched 3D morphologies of pathological human light chain proteins under reducing conditions. Colloids Surf B Biointerfaces 221:112983. https:\/\/doi.org\/10.1016\/j.colsurfb.2022.112983","journal-title":"Colloids Surf B Biointerfaces"},{"key":"1788_CR16","doi-asserted-by":"publisher","first-page":"1948","DOI":"10.1021\/bi00859a010","volume":"6","author":"H Edelhoch","year":"1967","unstructured":"Edelhoch H (1967) Spectroscopic determination of tryptophan and tyrosine in proteins. Biochemistry 6:1948\u20131954. https:\/\/doi.org\/10.1021\/bi00859a010","journal-title":"Biochemistry"},{"key":"1788_CR17","doi-asserted-by":"publisher","first-page":"1950","DOI":"10.1021\/bi00845a045","volume":"7","author":"GM Edelman","year":"1968","unstructured":"Edelman GM, Gall WEinar, Waxdal MJ, Konigsberg WH (1968) The covalent structure of a human \u03b3G-immunoglobulin. I. Isolation and characterization of the whole molecule, the polypeptide chains, and the tryptic fragments. Biochemistry 7:1950\u20131958. https:\/\/doi.org\/10.1021\/bi00845a045","journal-title":"Biochemistry"},{"key":"1788_CR18","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1042\/bj0880220","volume":"88","author":"J Fleischman","year":"1963","unstructured":"Fleischman J, Porter R, Press E (1963) The arrangement of the peptide chains in \u03b3-globulin. Biochem J 88:220\u2013228. https:\/\/doi.org\/10.1042\/bj0880220","journal-title":"Biochem J"},{"key":"1788_CR19","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1016\/S1359-0278(96)00059-4","volume":"1","author":"C Frisch","year":"1996","unstructured":"Frisch C, Kolmar H, Schmidt A et al (1996) Contribution of the intramolecular disulfide bridge to the folding stability of REIv, the variable domain of a human immunoglobulin \u03ba light chain. Fold des 1:431\u2013440. https:\/\/doi.org\/10.1016\/S1359-0278(96)00059-4","journal-title":"Fold des"},{"key":"1788_CR20","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-031-10256-1","volume-title":"Renal physiology and hydrosaline metabolism","author":"PA Gallardo","year":"2022","unstructured":"Gallardo PA, Vio CP (2022) Renal physiology and hydrosaline metabolism. Springer International Publishing, Cham"},{"key":"1788_CR21","doi-asserted-by":"publisher","first-page":"1287","DOI":"10.1016\/0006-291X(70)90227-5","volume":"41","author":"GG Glenner","year":"1970","unstructured":"Glenner GG, Harbaugh J, Ohms JI et al (1970) An amyloid protein: the amino-terminal variable fragment of an immunoglobulin light chain. Biochem Biophys Res Commun 41:1287\u20131289. https:\/\/doi.org\/10.1016\/0006-291X(70)90227-5","journal-title":"Biochem Biophys Res Commun"},{"key":"1788_CR22","doi-asserted-by":"publisher","first-page":"1433","DOI":"10.1093\/oxfordjournals.jbchem.a132661","volume":"86","author":"Y Goto","year":"1979","unstructured":"Goto Y, Hamaguchi K (1979) The role of the intrachain disulfide bond in the conformation and stability of the constant fragment of the immunoglobulin light chain1. J Biochem 86:1433\u20131441. https:\/\/doi.org\/10.1093\/oxfordjournals.jbchem.a132661","journal-title":"J Biochem"},{"key":"1788_CR23","doi-asserted-by":"publisher","first-page":"2876","DOI":"10.1038\/nprot.2006.202","volume":"1","author":"NJ Greenfield","year":"2006","unstructured":"Greenfield NJ (2006) Using circular dichroism spectra to estimate protein secondary structure. Nat Protoc 1:2876\u20132890. https:\/\/doi.org\/10.1038\/nprot.2006.202","journal-title":"Nat Protoc"},{"key":"1788_CR24","doi-asserted-by":"publisher","first-page":"9531","DOI":"10.3390\/ijms24119531","volume":"24","author":"M Gudowska-Sawczuk","year":"2023","unstructured":"Gudowska-Sawczuk M, Mroczko B (2023) Free light chains \u03ba and \u03bb as new biomarkers of selected diseases. IJMS 24:9531. https:\/\/doi.org\/10.3390\/ijms24119531","journal-title":"IJMS"},{"key":"1788_CR25","unstructured":"Janeway C (2001) Immunobiology: the immune system in health and disease. Garland Science"},{"key":"1788_CR26","doi-asserted-by":"crossref","unstructured":"Jones HB (1848) III. On a new substance occurring in the urine of a patient with mollities ossium. Philos Trans R Soc Lond 55\u201362","DOI":"10.1098\/rstl.1848.0003"},{"key":"1788_CR27","doi-asserted-by":"publisher","first-page":"882","DOI":"10.1002\/ajh.23773","volume":"89","author":"B Kaplan","year":"2014","unstructured":"Kaplan B, Golderman S, Aizenbud B et al (2014) Immunoglobulin-free light chain monomer-dimer patterns help to distinguish malignant from premalignant monoclonal gammopathies: a pilot study. Am J Hematol 89:882\u2013888. https:\/\/doi.org\/10.1002\/ajh.23773","journal-title":"Am J Hematol"},{"key":"1788_CR28","doi-asserted-by":"publisher","first-page":"726","DOI":"10.1100\/tsw.2011.65","volume":"11","author":"B Kaplan","year":"2011","unstructured":"Kaplan B, Livneh A, Sela B-A (2011) Immunoglobulin free light chain dimers in human diseases. Sci World J 11:726\u2013735. https:\/\/doi.org\/10.1100\/tsw.2011.65","journal-title":"Sci World J"},{"key":"1788_CR29","doi-asserted-by":"publisher","first-page":"552","DOI":"10.1021\/bi00622a032","volume":"16","author":"M Klein","year":"1977","unstructured":"Klein M, Kells DIC, Tinker DO, Dorrington KJ (1977) Thermodynamic and conformational studies on an immunoglobulin light chain which reversibly precipitates at low temperatures. Biochemistry 16:552\u2013560. https:\/\/doi.org\/10.1021\/bi00622a032","journal-title":"Biochemistry"},{"key":"1788_CR30","doi-asserted-by":"publisher","first-page":"2127172","DOI":"10.1080\/19420862.2022.2127172","volume":"14","author":"MJ Knight","year":"2022","unstructured":"Knight MJ, Floret L, Patel N et al (2022) The impact of forced degradation conditions on mAb dimer formation and subsequent influence on aggregation propensity. Mabs 14:2127172. https:\/\/doi.org\/10.1080\/19420862.2022.2127172","journal-title":"Mabs"},{"key":"1788_CR31","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1182\/blood-2016-10-743997","volume":"129","author":"TV Kourelis","year":"2017","unstructured":"Kourelis TV, Dasari S, Theis JD et al (2017) Clarifying immunoglobulin gene usage in systemic and localized immunoglobulin light-chain amyloidosis by mass spectrometry. Blood 129:299\u2013306. https:\/\/doi.org\/10.1182\/blood-2016-10-743997","journal-title":"Blood"},{"key":"1788_CR32","doi-asserted-by":"crossref","unstructured":"Krayukhina E, Uchiyama S (2016) Analytical ultracentrifugation. In: Senda T, Maenaka K (eds) Advanced methods in structural biology. Springer Japan, Tokyo, pp 165\u2013183","DOI":"10.1007\/978-4-431-56030-2_10"},{"key":"1788_CR33","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.22585","author":"S Kundu","year":"2022","unstructured":"Kundu S, Jha SB, Rivera AP et al (2022) Multiple myeloma and renal failure: mechanisms, diagnosis, and management. Cureus. https:\/\/doi.org\/10.7759\/cureus.22585","journal-title":"Cureus"},{"key":"1788_CR34","doi-asserted-by":"publisher","first-page":"1035","DOI":"10.1046\/j.1365-2141.2000.02318.x","volume":"111","author":"RA Kyle","year":"2000","unstructured":"Kyle RA (2000) Multiple myeloma: an odyssey of discovery. Br J Haematol 111:1035\u20131044. https:\/\/doi.org\/10.1046\/j.1365-2141.2000.02318.x","journal-title":"Br J Haematol"},{"key":"1788_CR35","unstructured":"Laue TM (1992) Computer-aided interpretation of analytical sedimentation data for proteins. Anal Ultracentrif Biochem Polym Sci 90\u2013125"},{"key":"1788_CR36","doi-asserted-by":"publisher","first-page":"1117","DOI":"10.1016\/j.kint.2020.02.010","volume":"97","author":"AS Levey","year":"2020","unstructured":"Levey AS, Eckardt K-U, Dorman NM et al (2020) Nomenclature for kidney function and disease: report of a Kidney Disease: Improving Global Outcomes (KDIGO) consensus conference. Kidney Int 97:1117\u20131129. https:\/\/doi.org\/10.1016\/j.kint.2020.02.010","journal-title":"Kidney Int"},{"key":"1788_CR37","doi-asserted-by":"publisher","first-page":"836","DOI":"10.1039\/C8BM00066B","volume":"6","author":"C Li","year":"2018","unstructured":"Li C, Xu L, Zuo YY, Yang P (2018) Tuning protein assembly pathways through superfast amyloid-like aggregation. Biomater Sci 6:836\u2013841. https:\/\/doi.org\/10.1039\/C8BM00066B","journal-title":"Biomater Sci"},{"key":"1788_CR38","doi-asserted-by":"publisher","first-page":"17","DOI":"10.4161\/mabs.4.1.18347","volume":"4","author":"H Liu","year":"2012","unstructured":"Liu H, May K (2012) Disulfide bond structures of IgG molecules: structural variations, chemical modifications and possible impacts to stability and biological function. Mabs 4:17\u201323. https:\/\/doi.org\/10.4161\/mabs.4.1.18347","journal-title":"Mabs"},{"key":"1788_CR39","doi-asserted-by":"publisher","first-page":"837","DOI":"10.1016\/j.jasms.2010.01.016","volume":"21","author":"P Liu","year":"2010","unstructured":"Liu P, O\u2019Mara BW, Warrack BM et al (2010) A tris (2-carboxyethyl) phosphine (TCEP) related cleavage on cysteine-containing proteins. J Am Soc Mass Spectrom 21:837\u2013844. https:\/\/doi.org\/10.1016\/j.jasms.2010.01.016","journal-title":"J Am Soc Mass Spectrom"},{"key":"1788_CR40","doi-asserted-by":"publisher","first-page":"2305","DOI":"10.1021\/acs.jpcb.8b12511","volume":"123","author":"DL Melnikova","year":"2019","unstructured":"Melnikova DL, Skirda VD, Nesmelova IV (2019) Effect of reducing agent TCEP on translational diffusion and supramolecular assembly in aqueous solutions of \u03b1-casein. J Phys Chem B 123:2305\u20132315. https:\/\/doi.org\/10.1021\/acs.jpcb.8b12511","journal-title":"J Phys Chem B"},{"key":"1788_CR41","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1038\/s41572-018-0034-3","volume":"4","author":"G Merlini","year":"2018","unstructured":"Merlini G, Dispenzieri A, Sanchorawala V et al (2018) Systemic immunoglobulin light chain amyloidosis. Nat Rev Dis Primers 4:38. https:\/\/doi.org\/10.1038\/s41572-018-0034-3","journal-title":"Nat Rev Dis Primers"},{"key":"1788_CR42","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1016\/j.ijcard.2009.04.044","volume":"145","author":"RQ Migrino","year":"2010","unstructured":"Migrino RQ, Hari P, Gutterman DD et al (2010) Systemic and microvascular oxidative stress induced by light chain amyloidosis. Int J Cardiol 145:67\u201368. https:\/\/doi.org\/10.1016\/j.ijcard.2009.04.044","journal-title":"Int J Cardiol"},{"key":"1788_CR43","doi-asserted-by":"crossref","unstructured":"Morgan G, Nau AN, Wong S, et al (2024) An updated AL-Base reveals ranked enrichment of immunoglobulin light chain variable genes in AL amyloidosis","DOI":"10.1101\/2024.09.11.612490"},{"key":"1788_CR44","doi-asserted-by":"publisher","first-page":"4280","DOI":"10.1016\/j.jmb.2016.08.021","volume":"428","author":"GJ Morgan","year":"2016","unstructured":"Morgan GJ, Kelly JW (2016) The kinetic stability of a full-length antibody light chain dimer determines whether endoproteolysis can release amyloidogenic variable domains. J Mol Biol 428:4280\u20134297. https:\/\/doi.org\/10.1016\/j.jmb.2016.08.021","journal-title":"J Mol Biol"},{"key":"1788_CR45","doi-asserted-by":"publisher","first-page":"8360","DOI":"10.1073\/pnas.1817567116","volume":"116","author":"GJ Morgan","year":"2019","unstructured":"Morgan GJ, Yan NL, Mortenson DE et al (2019) Stabilization of amyloidogenic immunoglobulin light chains by small molecules. Proc Natl Acad Sci USA 116:8360\u20138369. https:\/\/doi.org\/10.1073\/pnas.1817567116","journal-title":"Proc Natl Acad Sci USA"},{"key":"1788_CR46","doi-asserted-by":"publisher","first-page":"642","DOI":"10.1006\/bbrc.1998.9508","volume":"251","author":"KE Olsen","year":"1998","unstructured":"Olsen KE, Sletten K, Westermark P (1998) Fragments of the constant region of immunoglobulin light chains are constituents of AL-amyloid proteins. Biochem Biophys Res Commun 251:642\u2013647. https:\/\/doi.org\/10.1006\/bbrc.1998.9508","journal-title":"Biochem Biophys Res Commun"},{"key":"1788_CR47","doi-asserted-by":"publisher","first-page":"22604","DOI":"10.3390\/ijms141122604","volume":"14","author":"T Poshusta","year":"2013","unstructured":"Poshusta T, Katoh N, Gertz M et al (2013) Thermal stability threshold for amyloid formation in light chain amyloidosis. IJMS 14:22604\u201322617. https:\/\/doi.org\/10.3390\/ijms141122604","journal-title":"IJMS"},{"key":"1788_CR48","doi-asserted-by":"publisher","first-page":"1518","DOI":"10.3390\/life13071518","volume":"13","author":"R R\u00edos-Tamayo","year":"2023","unstructured":"R\u00edos-Tamayo R, Krsnik I, G\u00f3mez-Bueno M et al (2023) AL amyloidosis and multiple myeloma: a complex scenario in which cardiac involvement remains the key prognostic factor. Life 13:1518. https:\/\/doi.org\/10.3390\/life13071518","journal-title":"Life"},{"key":"1788_CR49","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1046\/j.1432-1327.1999.00136.x","volume":"260","author":"A Roussel","year":"1999","unstructured":"Roussel A, Spinelli S, D\u00e9ret S et al (1999) The structure of an entire noncovalent immunoglobulin kappa light-chain dimer (Bence-Jones protein) reveals a weak and unusual constant domains association. Eur J Biochem 260:192\u2013199. https:\/\/doi.org\/10.1046\/j.1432-1327.1999.00136.x","journal-title":"Eur J Biochem"},{"key":"1788_CR50","doi-asserted-by":"publisher","first-page":"7807","DOI":"10.1038\/s41467-023-43443-4","volume":"14","author":"T Sakai","year":"2023","unstructured":"Sakai T, Mashima T, Kobayashi N et al (2023) Structural and thermodynamic insights into antibody light chain tetramer formation through 3D domain swapping. Nat Commun 14:7807. https:\/\/doi.org\/10.1038\/s41467-023-43443-4","journal-title":"Nat Commun"},{"key":"1788_CR51","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1007\/s40620-018-0492-4","volume":"32","author":"IJ Sathick","year":"2019","unstructured":"Sathick IJ, Drosou ME, Leung N (2019) Myeloma light chain cast nephropathy, a review. J Nephrol 32:189\u2013198. https:\/\/doi.org\/10.1007\/s40620-018-0492-4","journal-title":"J Nephrol"},{"key":"1788_CR52","doi-asserted-by":"publisher","first-page":"1606","DOI":"10.1016\/S0006-3495(00)76713-0","volume":"78","author":"P Schuck","year":"2000","unstructured":"Schuck P (2000) Size-distribution analysis of macromolecules by sedimentation velocity ultracentrifugation and lamm equation modeling. Biophys J 78:1606\u20131619. https:\/\/doi.org\/10.1016\/S0006-3495(00)76713-0","journal-title":"Biophys J"},{"key":"1788_CR53","doi-asserted-by":"publisher","DOI":"10.1201\/9781315367231","volume-title":"Sedimentation velocity analytical ultracentrifugation: discrete species and size-distributions of macromolecules and particles","author":"P Schuck","year":"2016","unstructured":"Schuck P (2016) Sedimentation velocity analytical ultracentrifugation: discrete species and size-distributions of macromolecules and particles. CRC Press"},{"key":"1788_CR54","doi-asserted-by":"publisher","first-page":"2005","DOI":"10.1016\/j.bpj.2009.12.4336","volume":"98","author":"P Schuck","year":"2010","unstructured":"Schuck P (2010) Sedimentation patterns of rapidly reversible protein interactions. Biophys J 98:2005\u20132013. https:\/\/doi.org\/10.1016\/j.bpj.2009.12.4336","journal-title":"Biophys J"},{"key":"1788_CR55","doi-asserted-by":"publisher","first-page":"1096","DOI":"10.1016\/S0006-3495(02)75469-6","volume":"82","author":"P Schuck","year":"2002","unstructured":"Schuck P, Perugini MA, Gonzales NR et al (2002) Size-distribution analysis of proteins by analytical ultracentrifugation: strategies and application to model systems. Biophys J 82:1096\u20131111. https:\/\/doi.org\/10.1016\/S0006-3495(02)75469-6","journal-title":"Biophys J"},{"key":"1788_CR56","doi-asserted-by":"publisher","DOI":"10.1201\/b19028","volume-title":"Basic principles of analytical ultracentrifugation","author":"P Schuck","year":"2016","unstructured":"Schuck P, Zhao H, Brautigam CA, Ghirlando R (2016) Basic principles of analytical ultracentrifugation. CRC Press"},{"key":"1788_CR57","doi-asserted-by":"publisher","first-page":"11916","DOI":"10.1039\/C9CP01846H","volume":"21","author":"MA Sequeira","year":"2019","unstructured":"Sequeira MA, Herrera MG, Dodero VI (2019) Modulating amyloid fibrillation in a minimalist model peptide by intermolecular disulfide chemical reduction. Phys Chem Chem Phys 21:11916\u201311923. https:\/\/doi.org\/10.1039\/C9CP01846H","journal-title":"Phys Chem Chem Phys"},{"key":"1788_CR58","doi-asserted-by":"publisher","first-page":"447","DOI":"10.3109\/00365517609054462","volume":"36","author":"K S\u00f6lling","year":"1976","unstructured":"S\u00f6lling K (1976) Polymeric forms of free light chains in serum from normal individuals and from patients with renal diseases. Scand J Clin Lab Invest 36:447\u2013452. https:\/\/doi.org\/10.3109\/00365517609054462","journal-title":"Scand J Clin Lab Invest"},{"key":"1788_CR59","doi-asserted-by":"publisher","first-page":"9547","DOI":"10.1073\/pnas.95.16.9547","volume":"95","author":"A Solomon","year":"1998","unstructured":"Solomon A, Weiss DT, Murphy CL et al (1998) Light chain-associated amyloid deposits comprised of a novel \u03ba constant domain. Proc Natl Acad Sci USA 95:9547\u20139551. https:\/\/doi.org\/10.1073\/pnas.95.16.9547","journal-title":"Proc Natl Acad Sci USA"},{"key":"1788_CR60","doi-asserted-by":"publisher","first-page":"e8771","DOI":"10.7717\/peerj.8771","volume":"8","author":"R Sternke-Hoffmann","year":"2020","unstructured":"Sternke-Hoffmann R, Boquoi A, Lopez Y, Niedenhoff D et al (2020) Biochemical and biophysical characterisation of immunoglobulin free light chains derived from an initially unbiased population of patients with light chain disease. PeerJ 8:e8771. https:\/\/doi.org\/10.7717\/peerj.8771","journal-title":"PeerJ"},{"key":"1788_CR61","doi-asserted-by":"publisher","DOI":"10.1186\/s12915-022-01506-w","volume":"21","author":"R Sternke-Hoffmann","year":"2023","unstructured":"Sternke-Hoffmann R, Pauly T, Norrild RK et al (2023) Widespread amyloidogenicity potential of multiple myeloma patient-derived immunoglobulin light chains. BMC Biol 21:21. https:\/\/doi.org\/10.1186\/s12915-022-01506-w","journal-title":"BMC Biol"},{"key":"1788_CR62","doi-asserted-by":"publisher","DOI":"10.1186\/s12882-021-02250-z","volume":"22","author":"L-J Sun","year":"2021","unstructured":"Sun L-J, Dong H-R, Xu X-Y et al (2021) Two kinds of rare light chain cast nephropathy caused by multiple myeloma: case reports and literature review. BMC Nephrol 22:42. https:\/\/doi.org\/10.1186\/s12882-021-02250-z","journal-title":"BMC Nephrol"},{"key":"1788_CR63","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1016\/j.tips.2008.01.004","volume":"29","author":"M Thio","year":"2008","unstructured":"Thio M, Blokhuis B, Nijkamp F, Redegeld F (2008) Free immunoglobulin light chains: a novel target in the therapy of inflammatory diseases. Trends Pharmacol Sci 29:170\u2013174. https:\/\/doi.org\/10.1016\/j.tips.2008.01.004","journal-title":"Trends Pharmacol Sci"},{"key":"1788_CR64","doi-asserted-by":"publisher","first-page":"4629","DOI":"10.1093\/emboj\/20.17.4629","volume":"20","author":"V Turk","year":"2001","unstructured":"Turk V (2001) New EMBO members\u2019 review: lysosomal cysteine proteases: facts and opportunities. EMBO J 20:4629\u20134633. https:\/\/doi.org\/10.1093\/emboj\/20.17.4629","journal-title":"EMBO J"},{"key":"1788_CR65","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1016\/j.bbapap.2011.10.002","volume":"1824","author":"V Turk","year":"2012","unstructured":"Turk V, Stoka V, Vasiljeva O et al (2012) Cysteine cathepsins: from structure, function and regulation to new frontiers. Biochimica Et Biophysica Acta (BBA) Proteins Proteomics 1824:68\u201388. https:\/\/doi.org\/10.1016\/j.bbapap.2011.10.002","journal-title":"Biochimica Et Biophysica Acta (BBA) Proteins Proteomics"},{"key":"1788_CR66","doi-asserted-by":"crossref","first-page":"3909","DOI":"10.1016\/S0021-9258(18)97128-0","volume":"240","author":"PH Von Hippel","year":"1965","unstructured":"Von Hippel PH, Wong KY (1965) On the conformational stability of globular proteins. The effects of various electrolytes and nonelectrolytes on the thermal ribonuclease transition. J Biol Chem 240:3909\u20133923","journal-title":"J Biol Chem"},{"key":"1788_CR67","doi-asserted-by":"publisher","first-page":"1679","DOI":"10.3390\/cells9071679","volume":"9","author":"T Yadati","year":"2020","unstructured":"Yadati T, Houben T, Bitorina A, Shiri-Sverdlov R (2020) The ins and outs of cathepsins: physiological function and role in disease management. Cells 9:1679. https:\/\/doi.org\/10.3390\/cells9071679","journal-title":"Cells"},{"key":"1788_CR68","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1159\/000442511","volume":"1","author":"P Yadav","year":"2015","unstructured":"Yadav P, Cook M, Cockwell P (2015) Current trends of renal impairment in multiple myeloma. Kidney Dis 1:241\u2013257. https:\/\/doi.org\/10.1159\/000442511","journal-title":"Kidney Dis"},{"key":"1788_CR69","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1016\/j.bbcan.2018.09.002","volume":"1870","author":"AE Yuzhalin","year":"2018","unstructured":"Yuzhalin AE, Lim SY, Kutikhin AG, Gordon-Weeks AN (2018) Dynamic matrisome: ECM remodeling factors licensing cancer progression and metastasis. Biochimica Et Biophysica Acta (BBA) Rev Cancer 1870:207\u2013228. https:\/\/doi.org\/10.1016\/j.bbcan.2018.09.002","journal-title":"Biochimica Et Biophysica Acta (BBA) Rev Cancer"},{"key":"1788_CR70","doi-asserted-by":"crossref","unstructured":"Zanetti M, Capra JD (eds) (1999) The antibodies, 1st edn. CRC Press","DOI":"10.1201\/9781482283617"}],"container-title":["European Biophysics Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00249-025-01788-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00249-025-01788-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00249-025-01788-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T19:14:38Z","timestamp":1761333278000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00249-025-01788-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8]]},"references-count":70,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2025,8]]}},"alternative-id":["1788"],"URL":"https:\/\/doi.org\/10.1007\/s00249-025-01788-2","relation":{},"ISSN":["0175-7571","1432-1017"],"issn-type":[{"value":"0175-7571","type":"print"},{"value":"1432-1017","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8]]},"assertion":[{"value":"20 December 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 July 2025","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 July 2025","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 August 2025","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}]}}