Abstract
Amyloid fibrils are a hallmark of neurodegenerative diseases and exhibit a conformational diversity that governs their pathological functions. Despite recent findings concerning the pathological role of their conformational diversity, the way in which the heterogeneous conformations of amyloid fibrils can be formed has remained elusive. Here, we show that microwave-assisted chemistry affects the self-assembly process of amyloid fibril formation, which results in their conformational heterogeneity. In particular, microwave-assisted chemistry allows for delicate control of the thermodynamics of the self-assembly process, which enabled us to tune the molecular structure of β-lactoglobulin amyloid fibrils. The heterogeneous conformations of amyloid fibrils, which can be tuned with microwave-assisted chemistry, are attributed to the microwave-driven thermal energy affecting the electrostatic interaction during the self-assembly process. Our study demonstrates how microwave-assisted chemistry can be used to gain insight into the origin of conformational heterogeneity of amyloid fibrils as well as the design principles showing how the molecular structures of amyloid fibrils can be controlled.
Highlights
Amyloid fibrils are a hallmark of neurodegenerative diseases and exhibit a conformational diversity that governs their pathological functions
Amyloid fibrils that are formed by protein aggregation have recently been reported to play a vital role in the pathogenesis of various diseases ranging from neurodegenerative diseases[1,2,3] (e.g., Alzheimer’s disease and Parkinson’s disease) to type II diabetes[4,5] and cardiovascular diseases[6]
We first report that microwave-assisted chemistry allows for understanding how heterogeneous conformations of amyloid fibrils can be formed because the microwave affects the thermodynamics of protein aggregation, which is responsible for the formation of amyloid fibrils
Summary
Amyloid fibrils are a hallmark of neurodegenerative diseases and exhibit a conformational diversity that governs their pathological functions. Despite the important role of protein aggregation on disease pathogenesis, it has not yet been fully understood how the self-assembly process, i.e., the protein aggregation mechanism, governs the molecular structures of protein aggregates such as amyloid fibrils In addition to their pathological role, amyloid fibrils have recently been reported to serve as biocompatible and functional materials. The structural feature of amyloid fibrils, such as steric zipper pattern[27,28], helical pattern[26], and length[25], is a key design parameter that determines the material properties of amyloid fibrils Despite these recent findings[7,18,19,20,22,23,24,25,26,27,28,29,30] of the important role that the structure (conformation) of amyloid fibrils plays in their biological functions and material properties, it is not well understood how the molecular structures and conformational diversity of amyloid fibrils are determined
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