Not just a fluidifying effect: omega-3 phospholipids induce formation of non-lamellar structures in biomembranes. Issue 46 (9th November 2020)

• Record Type: Journal Article
• Authors: de Santis, Augusta; Vitiello, Giuseppe; Appavou, Marie-Sousai; Scoppola, Ernesto; Fragneto, Giovanna; Barnsley, Lester C.; Clifton, Luke A.; Ottaviani, Maria Francesca; Paduano, Luigi; Russo Krauss, Irene; D'Errico, Gerardino
• Is Part Of: Soft matter. Volume 16:Issue 46(2020)
• Page Start: 10425
• Page End: 10438
• Publication Date: 2020-11-09
• Subjects: Soft condensed matter -- Periodicals; 530.413
• DOI: 10.1039/d0sm01549k
• Languages: English
• ISSNs: 1744-683X

Abstract

Abstract : Beyond a threshold concentration, omega-3 phospholipid 22:6-22:6PC hampers the formation of a typical lamellar phase of lipid membranes forming small spherical aggregates. Abstract : Polyunsaturated omega-3 fatty acid docosahexaenoic acid (DHA) is found in very high concentrations in a few peculiar tissues, suggesting that it must have a specialized role. DHA was proposed to affect the function of the cell membrane and related proteins through an indirect mechanism of action, based on the DHA-phospholipid effects on the lipid bilayer structure. In this respect, most studies have focused on its influence on lipid-rafts, somehow neglecting the analysis of effects on liquid disordered phases that constitute most of the cell membranes, by reporting in these cases only a general fluidifying effect. In this study, by combining neutron reflectivity, cryo-transmission electron microscopy, small angle neutron scattering, dynamic light scattering and electron paramagnetic resonance spectroscopy, we characterize liquid disordered bilayers formed by the naturally abundant 1-palmitoyl-2-oleoyl- sn-glycero -3-phosphocholine and different contents of a di-DHA glycero -phosphocholine, 22:6-22:6PC, from both a molecular/microscopic and supramolecular/mesoscopic viewpoint. We show that, below a threshold concentration of about 40% molar percent, incorporation of 22:6-22:6PC in the membrane increases the lipid dynamics slightly but sufficiently to promote the membrane deformation and increase of multilamellarity. Notably, beyond this threshold, 22:6-22:6PC disfavours the formation of lamellar phases, leading to a phase separation consisting mostly of small spherical particles that coexist with a minority portion of a lipid blob with water-filled cavities. Concurrently, from a molecular viewpoint, the polyunsaturated acyl chains tend to fold and expose the termini to the aqueous medium. We propose that this peculiar tendency is a key feature of the DHA-phospholipids making them able to modulate the local morphology of biomembranes.