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

Abstract

<div> <div> <div><div><div><p>Artificial native-like lipid bilayer systems constructed from phospholipids assembling into unilamellar liposomes allow the reconstitution of detergent-solubilized transmembrane proteins into supramolecular lipid-protein assemblies called proteoliposomes, which mimic cellular membranes. Stabilization of these complexes remains challenging because of their chemical composition, the hydrophobicity and structural instability 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 supramolecular complexes can be successfully generated and immobilized within zeolitic-imidazole framework (ZIF) to enhance their stability against chemical and physical stressors. Upon immobilization in ZIF bio-composites, blank liposomes, and model transmembrane metal transporters in detergent micelles or embedded in proteoliposomes resist elevated temperatures, exposure to chemical denaturants, aging, and mechanical stresses. Extensive morphological and functional charac- terization 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.</p></div></div></div> </div> </div>

App-based quantification of crystal phases and amorphous content in ZIF biocomposites

“…1,2 Recent progress on composites based on MOFs and biomacromolecules, namely MOF biocomposites, have been generating significant interest in the field of biotechnology and biomedicine. [3][4][5][6] In particular, Zeolitic Imidazolate Frameworks (ZIFs) prepared from Zn 2+ and 2-methylimidazole (HmIm) are widely studied because their facile synthesis is compatible with several different classes of biomacromolecules (e.g. proteins, carbohydrates, lipids, nucleic acids, viruses, and cells).…”

“…proteins, carbohydrates, lipids, nucleic acids, viruses, and cells). [3][4][5][7][8][9][10][11] By mixing biomacromolecules to an aqueous solution of Zn 2+ cations and HmIM, it is possible to find conditions inducing the spontaneous formation of the ZIF material around biomacromolecules (i.e. biomimetic mineralization).…”

App-based Quantification of Crystal Phases and Amorphous Content in ZIFs Biocomposites

“…1,2 Recent progress on composites based on MOFs and biomacromolecules, namely MOF biocomposites, have been generating significant interest in the field of biotechnology and biomedicine. [3][4][5][6] In particular, Zeolitic Imidazolate Frameworks (ZIFs) prepared from Zn 2+ and 2-methylimidizaole (HmIm) are widely studied because their facile synthesis is compatible with several different classes of biomacromolecules (e.g. proteins, carbohydrates, lipids, nucleic acids, viruses, and cells).…”

“…proteins, carbohydrates, lipids, nucleic acids, viruses, and cells). [3][4][5][7][8][9][10][11] By mixing biomacromlecules to a an aqueous solution of Zn cations and HmIM, it is possible to find conditions inducing the spontaneous formation of the ZIF material around biomacromolecules (i.e. biomimetic mineralization).…”

“…biomimetic mineralization). 3 Once the ZIF biocomposite (biomacromolecule@ZIF) is formed, the encapsulated biomacromolecule can be protected against harsh environments 3,12 , can be stored without the need of refrigeration for long periods 5,9,12 and can be released in a controlled fashion by exposing the biocomposite to chelating agents (e.g. EDTA) 13 , acidic environments (e.g., pH≤6.5) 13,14 and buffer solutions (e.g., PBS) [13][14][15] .…”