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Not just a fluidifying effect: omega-3 phospholipids induce formation of non-lamellar structures in biomembranes


The polyunsaturated omega-3 fatty acid docosaHexaenoic Acid (DHA) is found in very high concentration in a few peculiar tissues suggesting 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. Here, 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-oleyl-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 lipid dynamics slightly but sufficiently to promote membrane deformation and increase of multilamellarity. Notably, beyond this threshold, 22:6-22:6PC disfavours 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.

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Article information

27 Aug 2020
15 Oct 2020
First published
16 Oct 2020

Soft Matter, 2020, Accepted Manuscript
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Not just a fluidifying effect: omega-3 phospholipids induce formation of non-lamellar structures in biomembranes

A. De Santis, G. Vitiello, M. Appavou, E. Scoppola, G. Fragneto, L. C. Barnsley, L. A. Clifton, M. F. Ottaviani, L. Paduano, I. Russo Krauss and G. D'Errico, Soft Matter, 2020, Accepted Manuscript , DOI: 10.1039/D0SM01549K

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