Abstract
Structural properties of plasmenyl-glycerophospholipids (plasmalogens) have been scarcely studied for plasmalogens with long polyunsaturated fatty acid (PUFA) chains, despite of their significance for the organization and functions of the cellular membranes. Elaboration of supramolecular assemblies involving PUFA-chain plasmalogens in nanostructured mixtures with lyotropic lipids may accelerate the development of nanomedicines for certain severe pathologies (e.g., peroxisomal disorders, cardiometabolic impairments, and neurodegenerative Alzheimer’s and Parkinson’s diseases). Here, we investigate the spontaneous self-assembly of bioinspired, custom-produced docosapentaenoyl (DPA) plasmenyl (ether) and ester phospholipids in aqueous environment (pH 7) by synchrotron small-angle X-ray scattering (SAXS) and cryogenic transmission electron microscopy (cryo-TEM). A coexistence of a liquid crystalline primitive cubic Im3m phase and an inverted hexagonal (HII) phase is observed for the DPA-ethanolamine plasmalogen (C16:1p-22:5n6 PE) derivative. A double-diamond cubic Pn3m phase is formed in mixed assemblies of the phosphoethanolamine plasmalogen (C16:1p-22:5n6 PE) and monoolein (MO), whereas a coexistence of cubic and lamellar liquid crystalline phases is established for the DPA-plasmenyl phosphocholine (C16:1p-22:5n6 PC)/MO mixture at ambient temperature. The DPA-diacyl phosphoinositol (22:5n6-22:5n6 PI) ester lipid displays a propensity for a lamellar phase formation. Double membrane vesicles and multilamellar onion topologies with inhomogeneous distribution of interfacial curvature are formed upon incorporation of the phosphoethanolamine plasmalogen (C16:1p-22:5n6 PE) into dioleoylphosphocholine (DOPC) bilayers. Nanoparticulate formulations of plasmalogen-loaded cubosomes, hexosomes, and various multiphase cubosome- and hexosome-derived architectures and mixed type nano-objects (e.g., oil droplet-embedding vesicles or core–shell particles with soft corona) are produced with PUFA-chain phospholipids and lipophilic antioxidant-containing membrane compositions that are characterized by synchrotron SAXS and cryo-TEM imaging. The obtained multiphase nanostructures reflect the changes in the membrane curvature induced by the inclusion of DPA-based PE and PC plasmalogens, as well as DPA-PI ester derivative, and open new opportunities for exploration of these bioinspired nanoassemblies.
Highlights
We report here a structural study of novel custom-synthesized plasmenyl and ester phospholipids with long polyunsaturated fatty acid (PUFA) (22:5n6) chains
A coexistence of a liquid crystalline primitive cubic Im3m phase with an inverted hexagonal (HII) phase is identified at a temperature of 22◦C for the freshly prepared bulk-phase docosapentaenoic acid (DPA)-ethanolamine plasmalogen (C16:1p-22:5n6 PE)/water system (Figure 3A, plot 1)
The use of the first isomer (DPA, C22:5n6) in the present work for the design of PUFAplasmalogens or ester species is motivated by the increased percentage of DPA (C22:5n6) derivatives found in biological cubic membrane structures (Deng et al, 2009)
Summary
Plasmenyl-phospholipids (plasmalogens) are a class of ethertype (1-alkyl-1 -enyl, 2-acyl) glycerophospholipids with essential functions for the living cells in the brain, retina, heart, lung, skeletal muscles, and testis (Gross, 1985; Creuwels et al, 1997; Batenburg and Haagsman, 1998; Snyder, 1999; Goldfine, 2010; Wallner and Schmitz, 2011; Saab et al, 2014; Dean and Lodhi, 2018; Jiménez-Rojo and Riezman, 2019; Paul et al, 2019). The arrangement of lipids and amphiphiles in supramolecular assemblies is governed by intermolecular hydrophobic and electrostatic interactions, temperature, degree of hydration, and the geometry of the molecules (Israelachvili et al, 1976; Cullis and de Kruijff, 1979; Cui et al, 2007; Shaharabani et al, 2016)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
