Cell-Membrane-Mimicking Lipid-Coated Nanoparticles Confer Raman Enhancement to Membrane Proteins and Reveal Membrane-Attached Amyloid-beta Conformation

Bhowmik, Debanjan and Mote, Kaustubh R and MacLaughlin, Christina M and Biswas, Nupur and Chandra, Bappaditya and Basu, Jaydeep K and Walker, Gilbert C and Madhu, Perunthiruthy K and Maiti, Sudipta (2015) Cell-Membrane-Mimicking Lipid-Coated Nanoparticles Confer Raman Enhancement to Membrane Proteins and Reveal Membrane-Attached Amyloid-beta Conformation. In: ACS NANO, 9 (9). pp. 9070-9077.

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Abstract

Identifying the structures of membrane bound proteins is critical to understanding their function in healthy and diseased states. We introduce a surface enhanced Raman spectroscopy technique which can determine the conformation of membrane-bound proteins, at low micromolar concentrations, and also in the presence of a substantial membrane-free fraction. Unlike conventional surface enhanced Raman spectroscopy, our approach does not require immobilization of molecules, as it uses spontaneous binding of proteins to lipid bilayer-encapsulated Ag nanoparticles. We apply this technique to probe membrane-attached oligomers of Amyloid-beta(40) (A beta(40)), whose conformation is keenly sought in the context of Alzheimer's disease. Isotope-shifts in the Raman spectra help us obtain secondary structure information at the level of individual residues. Our results show the presence of a beta-turn, flanked by two beta-sheet regions. We use solid-state NMR data to confirm the presence of the beta-sheets in these regions. In the membrane-attached oligomer, we find a strongly contrasting and near-orthogonal orientation of the backbone H-bonds compared to what is found in the mature, less-toxic A beta fibrils. Significantly, this allows a ``porin'' like beta-barrel structure, providing a structural basis for proposed mechanisms of A beta oligomer toxicity.

Item Type:	Journal Article
Publication:	ACS NANO
Publisher:	AMER CHEMICAL SOC
Additional Information:	Copy right for this article belongs to the AMER CHEMICAL SOC, 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
Keywords:	amyloid beta peptide; oligomers; surface enhanced Raman spectroscopy; membrane protein structures; solid-state NMR; lipid SERS; lipid-coated nanoparticles
Department/Centre:	Division of Physical & Mathematical Sciences > Physics
Date Deposited:	30 Oct 2015 07:05
Last Modified:	30 Oct 2015 07:05
URI:	http://eprints.iisc.ac.in/id/eprint/52646

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