Microfluidic Diffusion Platform for Characterizing the Sizes of Lipid Vesicles and the Thermodynamics of Protein-Lipid Interactions

Analytical Chemistry
Hongze GangTuomas P J Knowles

Abstract

Elucidation of the fundamental interactions of proteins with biological membranes under native conditions is crucial for understanding the molecular basis of their biological function and malfunction. Notably, the large surface to volume ratio of living cells provides a molecular landscape for significant interactions of cellular components with membranes, thereby potentially modulating their function. However, such interactions can be challenging to probe using conventional biophysical methods due to the heterogeneity of the species and processes involved. Here, we use direct measurements of micron scale molecular diffusivity to detect and quantify the interactions of α-synuclein, associated with the etiology of Parkinson's disease, with negatively charged lipid vesicles. We further demonstrate that this microfluidic approach enables the characterization of size distributions of different binary mixtures of vesicles, which are not readily accessible using conventional light scattering techniques. Finally, the size distributions of the two α-synuclein conformations, free α-synuclein and membrane-bound α-synuclein, were resolved under varying lipid:protein ratios, thus, allowing the determination of the dissociation constant and...Continue Reading

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Citations

Mar 19, 2020·International Journal of Molecular Sciences·Rebecca Sternke-HoffmannAlexander K Buell
Aug 4, 2020·Lab on a Chip·Yuewen ZhangTuomas P J Knowles
Dec 15, 2019·Biomolecules·Tomas SneiderisVytautas Smirnovas
Dec 30, 2020·Biochimica Et Biophysica Acta. Biomembranes·Greta MusteikytėTuomas P J Knowles
Feb 5, 2021·The Journal of Physical Chemistry. B·Brandon M HooverRegina M Murphy
Apr 9, 2021·Current Opinion in Structural Biology·Daniel E OtzenHenrik Jensen
Feb 18, 2020·Biochimica Et Biophysica Acta. Biomembranes·Mehdi AzouzAlexandre Ciaccafava

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