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Ultrasensitive Detection of Lipid-Induced Misfolding of the Prion Protein at the Aqueous–Liquid Crystal Interface

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Version 2 2024-02-19, 21:46
Version 1 2024-02-16, 13:36
journal contribution
posted on 2024-02-19, 21:46 authored by Tarang Gupta, Lisha Arora, Samrat Mukhopadhyay, Santanu Kumar Pal
The misfolding of the α-helical cellular prion protein into a self-propagating β-rich aggregated form is a key pathogenic event in fatal and transmissible neurodegenerative diseases collectively known as prion diseases. Herein, we utilize the interfacial properties of liquid crystals (LCs) to monitor the lipid-membrane-induced conformational switching of prion protein (PrP) into β-rich amyloid fibrils. The lipid-induced conformational switching resulting in aggregation occurs at the nanomolar protein concentration and is primarily mediated by electrostatic interactions between PrP and lipid headgroups. Our LC-based methodology offers a potent and sensitive tool to detect and delineate molecular mechanisms of PrP misfolding mediated by lipid–protein interactions at the aqueous interface under physiological conditions.

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