The effect of hydroxylated fatty acid-containing phospholipids in the remodeling of lipid membranes

• Published in: Biochimica et biophysica acta 2014-06, Vol.1838 (6), p.1509-1517
• Main Authors: Piotto, Stefano, Trapani, Alfonso, Bianchino, Erminia, Ibarguren, Maitane, López, David J., Busquets, Xavier, Concilio, Simona
• Format: Article
• Language: English
• Subjects: 2OHOA; Animals; Cell Membrane - chemistry; Fatty Acids - chemistry; Humans; Lipid Bilayers - chemistry; Lipid membrane; Membrane Lipids - chemistry; Membrane Microdomains; Membrane physical state; Molecular dynamics; Oleic Acids - chemistry; Phospholipids - chemistry
• ISSN: 0005-2736; 0006-3002; 1879-2642
• DOI: 10.1016/j.bbamem.2014.01.014

The synthetic fatty acid 2-hydroxyoleic acid (2OHOA) is an antitumor drug that regulates membrane lipid composition and structure. An important effect of this drug is the restoration of sphingomyelin (SM) levels in cancer cell membranes, where the SM concentration is lower than in non-tumor cells. It is well known that free fatty acid concentration in cell membranes is lower than 5%, and that fatty acid excess is rapidly incorporated into phospholipids. In a recent work, we have considered the effect of free 2OHOA in model membranes in liquid ordered (Lo) and liquid disordered (Ld) phases, by using all-atom molecular dynamics. This study concerns membranes that are modified upon incorporation of 2OHOA into different phospholipids. 2OHOA-containing phospholipids have a permanent effect on lipid membranes, making a Ld membrane surface more compact and less hydrated, whereas the opposite effect is observed in Lo domains. Moreover, the hydroxyl group of fatty acid chains increases the propensity of Ld model membranes to form hexagonal or other non-lamellar structures. This article is part of a Special Issue entitled: Membrane Structure and Function: Relevance in the Cell's Physiology, Pathology and Therapy. [Display omitted] •Incorporation of 2OHOA renders a Ld membrane surface more compact and less hydrated.•Incorporation of 2OHOA renders Lo domains less compact and more hydrated.•2OHOA in Ld membranes may favor the emergence of non-lamellar structures.•The boundaries between Lo and Ld domains are modified upon incorporation of 2OHOA.•The presence of an OH group in POPC induces CHOL leakage from lipid rafts.