polyglutamine, amyloid, oligomer, lipid bilayer, solution AFM, fluorescence microscopy
Digital Object Identifier (DOI)
Lipid membranes are suggested as the primary target of amyloid aggregates. We study aggregates formed by a polyglutamine (polyQ) peptide, and their disruptive effect on lipid membranes. Using solution atomic force microscopy (AFM), we observe polyQ oligomers coexisting with short fibrils, which have a twisted morphology that likely corresponds to two intertwined oligomer strings. Fourier transform infrared spectroscopy reveals that the content of β-sheet enriched aggregates increases with incubation time. Using fluorescence microscopy, we find that exposure to polyQ aggregates results in deflated morphology of giant unilamellar vesicles. PolyQ aggregates induced membrane disruption is further substantiated by time-dependent calcein leakage from the interior to the exterior of lipid vesicles. Detailed structural and mechanical perturbations of lipid membranes are revealed by solution AFM. We find that membrane disruption by polyQ aggregates proceeds by a two-step process, involving partial and full disruption. In addition to height contrast, the resulting partially and fully disrupted bilayers have distinct rigidity and adhesion force properties compared to the intact bilayer. Specifically, the bilayer rigidity increases as the intact bilayer becomes partially and fully disrupted. Surprisingly, the adhesion force first decreases and then increases during the disruption process. By resolving individual fibrils deposited on bilayer surface, we show that both the length and the number of fibrils can increase with incubation time. Our results highlight that membrane disruption could be the molecular basis of polyQ aggregates induced cytotoxicity.
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Citation / Publisher Attribution
Biochimica et Biophysica Acta (BBA) - Biomembranes, v. 1858, issue 4, p. 661-670
This article is the post-print author version. Under a Creative Commons license.
Scholar Commons Citation
Sing Ho, Chian; Khadka, Nawal K.; She, Fengyu; Cai, Jianfeng; and Pan, Jianjun, "Polyglutamine Aggregates Impair Lipid Membrane Integrity and Enhance Lipid Membrane Rigidity" (2016). Physics Faculty Publications. 21.