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Stabilization of Supramolecular Membrane Protein-Lipid Bilayer Assemblies Through Immobilization in a Crystalline Exoskeleton

preprint
submitted on 20.07.2020 and posted on 22.07.2020 by Fabian C. Herbert, Sameera Abeyrathna, Nisansala Abeyrathna, Yalini Wijesundara, Olivia Brohlin, Michael A. Luzuriaga, Alejandra Durand-Silva, Shashini D. Diwakara, Ronald A. Smaldone, Gabriele Meloni, Jeremiah J. Gassensmith

Artificial native-like lipid bilayer systems constructed from phospholipids assembling into unilamel- lar liposomes allow the reconstitution of detergent-solubilized transmembrane proteins into supramolecular lipid-protein assemblies called proteoliposomes, which mimic cellular membranes. Stabilization of these com- plexes remains challenging because of their chemical composition, the hydrophobicity and structural instabil- ity of membrane proteins, and the lability of interactions between protein, detergent, and lipids within micelles and lipid bilayers. In this work we demonstrate that metastable lipid, protein-detergent, and protein-lipid su- pramolecular complexes can be successfully generated and immobilized within zeolitic-imidazole framework- 8 (ZIF-8) to enhance their stability against chemical and physical stressors. Upon immobilization in ZIF-8 bio- composites, blank liposomes, and model transmembrane metal transporters in detergent micelles or embed- ded in proteoliposomes resist elevated temperatures, exposure to chemical denaturants, aging, and mechanical stresses. Extensive morphological and functional characterization of the assemblies upon exfoliation reveal that all these complexes encapsulated within the framework maintain their native morphology, structure, and activity, which is otherwise lost rapidly without immobilization.

Funding

National Science Foundation [CAREER DMR- 1654405]

Welch Foundation [AT-1989- 20190330]

Welch Foundation (Grant: AT-1935-20170325)

National Institutes of Health R35GM128704

Army Research Laboratory (W911NF-18-2- 0035)

History

Email Address of Submitting Author

gassensmith@utdallas.edu

Institution

The University of Texas at Dallas

Country

United States

ORCID For Submitting Author

0000-0001-6400-8106

Declaration of Conflict of Interest

none

Version Notes

version 1, the first version.

Exports