Hierarchical Protofilament Intertwining Rules the Formation of Mixed-Curvature Amyloid Polymorphs
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Date
2024-08
Publication Type
Journal Article
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yes
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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.
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published
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Journal / series
Volume
11 (32)
Pages / Article No.
2402740
Publisher
Wiley-VCH
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Date collected
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Subject
amyloid polymorphism; atomic force microscopy; filament intertwining mechanism; mixed-curvature amyloid
Organisational unit
03857 - Mezzenga, Raffaele / Mezzenga, Raffaele
Notes
Funding
177195 - Molecular and Cellular Modulation in Parkinson's Disease (SNF)