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Not just a fluidifying effect: omega-3 phospholipids induce formation of non-lamellar structures in biomembranes
Soft Matter ( IF 2.9 ) Pub Date : 2020-10-16 , DOI: 10.1039/d0sm01549k
Augusta de Santis 1 , Giuseppe Vitiello , Marie-Sousai Appavou , Ernesto Scoppola , Giovanna Fragneto , Lester C Barnsley , Luke A Clifton , Maria Francesca Ottaviani , Luigi Paduano , Irene Russo Krauss , Gerardino D'Errico
Affiliation  

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.

中文翻译:

不仅具有流化作用:omega-3磷脂诱导生物膜中非薄片结构的形成

在一些特殊的组织中发现多不饱和的ω-3脂肪酸二十二碳六烯酸(DHA)的浓度很高,这表明它必须具有特殊的作用。基于DHA对脂质双层结构的影响,提出了DHA通过间接作用机制影响细胞膜和相关蛋白的功能。在这方面,大多数研究都集中在其对脂质筏的影响上,而忽略了对构成大多数细胞膜的液相紊乱相的影响的分析,因为在这些情况下仅报道了一般的流化作用。在这项研究中,通过结合中子反射率,低温透射电子显微镜,小角度中子散射,动态光散射和电子顺磁共振光谱,sn-甘油-3-磷酸胆碱和不同含量的di-DHA甘油从分子/微观和超分子/介观角度来看,β-磷酸胆碱22:6-22:6PC。我们显示,在约40%摩尔百分比的阈值浓度以下,膜中掺入22:6-22:6PC会稍微增加脂质动力学,但足以促进膜变形并增加多层性。值得注意的是,超过此阈值,22:6-22:6PC不利于层状相的形成,导致相分离,该相分离主要由与球形小颗粒共存的小球形颗粒组成,该小球形颗粒与充满水腔的脂质斑点共存。同时,从分子观点来看,多不饱和酰基链倾向于折叠并使末端暴露于水性介质。
更新日期:2020-11-09
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