Polyglutamine aggregates impair lipid membrane integrity and enhance lipid membrane rigidity

Biochimica Et Biophysica Acta
Chian Sing HoJianjun Pan

Abstract

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 ...Continue Reading

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Citations

May 12, 2016·The Journal of Physical Chemistry. B·Jianjun Pan, Nawal K Khadka
Jun 11, 2016·Langmuir : the ACS Journal of Surfaces and Colloids·Chian Sing HoJianjun Pan
Oct 4, 2017·Nucleic Acids Research·Lauren G DoumaLinda B Bloom
Feb 13, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Pathomwat WongrattanakamonSupat Jiranusornkul
Jan 31, 2017·Biochimica Et Biophysica Acta. Biomembranes·Nawal K KhadkaJianjun Pan
Apr 24, 2021·Biochimica Et Biophysica Acta. Biomembranes·Nawal K KhadkaLaxman Mainali
Feb 9, 2017·Biochemistry·Adewale AdegbuyiroJustin Legleiter

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