journal article·2024-08Open access

Hierarchical Protofilament Intertwining Rules the Formation of Mixed‐Curvature Amyloid Polymorphs

Jiangtao Zhou, Salvatore Assenza, Meltem Tatli, Jiawen Tian, Ioana M. Ilie, Eugene L. Starostin, Amedeo Caflisch, Tuomas P. J. Knowles, Giovanni Dietler, Francesco S. Ruggeri, Henning Stahlberg, Sergey K. Sekatskii, Raffaele Mezzenga

Advanced Science· Volume 11· Issue 32

Abstract

Abstract Amyloid polymorphism is a hallmark of almost all amyloid species, yet the mechanisms underlying the formation of amyloid polymorphs and their complex architectures remain elusive. Commonly, two main mesoscopic topologies are found in amyloid polymorphs characterized by non‐zero Gaussian and mean curvatures: twisted ribbons and helical fibrils, respectively. Here, a rich heterogeneity of configurations is demonstrated on insulin amyloid fibrils, where protofilament packing can occur, besides the common polymorphs, also in a combined mode forming mixed‐curvature polymorphs. Through AFM statistical analysis, an extended array of heterogeneous architectures that are rationalized by mesoscopic theoretical arguments are identified. Notably, an unusual fibrillization pathway is also unraveled toward mixed‐curvature polymorphs via the widespread recruitment and intertwining of protofilaments and protofibrils. The results present an original view of amyloid polymorphism and advance the fundamental understanding of the fibrillization mechanism from single protofilaments into mature amyloid fibrils.
Source: crossref · Quality: baseline

Research context

OpenAlex topics: Alzheimer's disease research and treatments · Prion Diseases and Protein Misfolding · Protein Structure and Dynamics

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Laboratory of Physics of Living Matter, Institute of Physics Ecole Polytechnique Fédérale de Lausanne (EPFL) Lausanne CH‐1015 Switzerland

Department of Health Sciences and Technology ETH Zurich Zurich Switzerland

Departamento de Física Teórica de la Materia Condensada Universidad Autónoma de Madrid Madrid 28049 Spain

Condensed Matter Physics Center (IFIMAC) Universidad Autónoma de Madrid Madrid 28049 Spain

Instituto Nicolás Cabrera Universidad Autónoma de Madrid Madrid 28049 Spain

Laboratory of Biological Electron Microscopy Institute of Physics SB EPFL and Dep. of Fund. Microbiol. Faculty of Biology and Medicine UNIL Rt. de la Sorge Lausanne 1015 Switzerland

van't Hoff Institute for Molecular Sciences University of Amsterdam P.O. Box 94157 Amsterdam 1090 GD The Netherlands

Amsterdam Center for Multiscale Modeling (ACMM) University of Amsterdam P.O. Box 94157 Amsterdam 1090 GD The Netherlands

Department of Civil Environmental & Geomatic Engineering University College London Gower Street London WC1E 6BT UK

Department of Biochemistry University of Zürich Zürich CH‐8057 Switzerland

Department of Chemistry University of Cambridge Lensfield Road Cambridge CB2 1EW UK

Laboratory of Organic Chemistry Wageningen University & Research Stippeneng 4 Wageningen 6703 WE The Netherlands

Physical Chemistry and Soft Matter Wageningen University & Research Stippeneng 4 Wageningen 6703 WE The Netherlands

Department of Materials ETH Zurich Zurich 8093 Switzerland

Funding

Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung

References (49)

Show source-provided references
1. 10.1146/annurev.biochem.75.101304.12390110.1146/annurev.biochem.75.101304.123901 ↗
2. 10.1016/j.jmb.2004.06.04310.1016/j.jmb.2004.06.043 ↗
3. 10.1038/s41467-018-03164-510.1038/s41467-018-03164-5 ↗
4. 10.1002/anie.20171341610.1002/anie.201713416 ↗
5. 10.1002/anie.20151152410.1002/anie.201511524 ↗
6. 10.1038/s41467-021-21129-z10.1038/s41467-021-21129-z ↗
7. 10.1073/pnas.14245939910.1073/pnas.142459399 ↗
8. 10.4161/auto.1904810.4161/auto.19048 ↗
9. 10.1038/nature2300210.1038/nature23002 ↗
10. 10.1016/j.jmb.2021.16712410.1016/j.jmb.2021.167124 ↗
11. 10.1038/s41467-019-12683-810.1038/s41467-019-12683-8 ↗
12. 10.1021/acsnano.9b0967610.1021/acsnano.9b09676 ↗
13. 10.1038/383685a010.1038/383685a0 ↗
14. 10.1038/nnano.2010.5910.1038/nnano.2010.59 ↗
15. 10.1021/bm200216u10.1021/bm200216u ↗
16. 10.1002/advs.20210444510.1002/advs.202104445 ↗
17. 10.1038/nnano.2015.31010.1038/nnano.2015.310 ↗
18. 10.1039/C6CS00542J10.1039/C6CS00542J ↗
19. 10.1038/s41565-018-0071-910.1038/s41565-018-0071-9 ↗
20. 10.1021/acsnano.2c1003910.1021/acsnano.2c10039 ↗
21. 10.1038/s41586-021-03911-710.1038/s41586-021-03911-7 ↗
22. 10.1038/nature1536810.1038/nature15368 ↗
23. 10.1126/science.aba352610.1126/science.aba3526 ↗
24. 10.1073/pnas.172122011510.1073/pnas.1721220115 ↗
25. 10.1039/C9CS00199A10.1039/C9CS00199A ↗
26. 10.1016/j.jcis.2015.11.03010.1016/j.jcis.2015.11.030 ↗
27. 10.1038/s41467-017-01424-410.1038/s41467-017-01424-4 ↗
28. 10.1038/nature2041610.1038/nature20416 ↗
29. 10.1039/C4CP05563B10.1039/C4CP05563B ↗
30. 10.1039/c0nr00840k10.1039/c0nr00840k ↗
31. 10.1073/pnas.120995511010.1073/pnas.1209955110 ↗
32. 10.1016/S0006-3495(03)74550-010.1016/S0006-3495(03)74550-0 ↗
33. 10.1073/pnas.091008010610.1073/pnas.0910080106 ↗
34. 10.1110/ps.9.10.196010.1110/ps.9.10.1960 ↗
35. 10.1021/nn406121w10.1021/nn406121w ↗
36. 10.1039/c1sm05382e10.1039/c1sm05382e ↗
37. 10.1038/nature0569510.1038/nature05695 ↗
38. 10.1038/nnano.2011.10210.1038/nnano.2011.102 ↗
39. 10.1166/jamr.2013.116410.1166/jamr.2013.1164 ↗
40. 10.1038/ncomms883110.1038/ncomms8831 ↗
41. 10.1021/acs.chemrev.6b0044810.1021/acs.chemrev.6b00448 ↗
42. 10.1038/nchem.261510.1038/nchem.2615 ↗
43. 10.1038/nmeth.416910.1038/nmeth.4169 ↗
44. 10.1016/j.jsb.2012.09.00610.1016/j.jsb.2012.09.006 ↗
45. 10.1016/j.jsb.2012.09.00610.1016/j.jsb.2012.09.006 ↗
46. 10.1042/BCJ2021070810.1042/BCJ20210708 ↗
47. 10.1016/j.jsb.2015.08.00810.1016/j.jsb.2015.08.008 ↗
48. 10.7554/eLife.7030710.7554/eLife.70307 ↗
49. 10.1038/nmeth.201910.1038/nmeth.2019 ↗