The effect of hydroxylated fatty acid-containing phospholipids in the remodeling of lipid membranes.
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.
Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132, Fisciano 84084, SA, Italy. Electronic address: piotto@unisa.it.
Stefano
S
Piotto
Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132, Fisciano 84084, SA, Italy.
Alfonso
A
Trapani
Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132, Fisciano 84084, SA, Italy; BIOGEM s.c.a.r.l. - Research Institute Gaetano Salvatore, Via camporeale - area P.I.P., 83031 Ariano Irpino, AV, Italy.
Erminia
E
Bianchino
Laboratory of Molecular Cell Biomedicine, University of the Balearic Islands - Lipopharma Therapeutics, S.L., Palma, Spain.
Maitane
M
Ibarguren
Laboratory of Molecular Cell Biomedicine, University of the Balearic Islands - Lipopharma Therapeutics, S.L., Palma, Spain.
David J
DJ
López
Laboratory of Molecular Cell Biomedicine, University of the Balearic Islands - Lipopharma Therapeutics, S.L., Palma, Spain.
Xavier
X
Busquets
Department of Industrial Engineering, University of Salerno, Via Giovanni Paolo II, 132, Fisciano 84084, SA, Italy.
Simona
S
Concilio
D000818:Animals; D002462:Cell Membrane / Q000737:chemistry*; D005227:Fatty Acids / Q000737:chemistry*; D006801:Humans; D008051:Lipid Bilayers / Q000737:chemistry*; D008563:Membrane Lipids / Q000737:chemistry*; D021962:Membrane Microdomains; D009829:Oleic Acids / Q000737:chemistry*; D010743:Phospholipids / Q000737:chemistry*
C483229:2-hydroxyoleic acid; D005227:Fatty Acids; D008051:Lipid Bilayers; D008563:Membrane Lipids; D009829:Oleic Acids; D010743:Phospholipids
2OHOA; Lipid membrane; Membrane physical state; Molecular dynamics