Membrane lipids: where they are and how they behave

Abstract

Throughout the biological world, a 30 Å hydrophobic film typically delimits the environments that serve as the margin between life and death for individual cells. Biochemical and biophysical findings have provided a detailed model of the composition and structure of membranes, which includes levels of dynamic organization both across the lipid bilayer (lipid asymmetry) and in the lateral dimension (lipid domains) of membranes. How do cells apply anabolic and catabolic enzymes, translocases and transporters, plus the intrinsic physical phase behaviour of lipids and their interactions with membrane proteins, to create the unique compositions and multiple functionalities of their individual membranes?From the ongoing cataloguing of lipid structures (lipidomics), it is clear that eukaryotic cells invest substantial resources in generating thousands of different lipids 1 . Why do cells use ~5% of their genes to synthesize all of these lipids? The fundamental biological maxim that 'structure subserves function' implies that there must be evolutionary advantages that are dependent on a complex lipid repertoire. Although we now understand the specific functions of numerous lipids, the full definition of the utility of the eukaryotic lipid repertoire remains elusive.Lipids fulfil three general functions. First, because of their relatively reduced state, lipids are used for energy storage, principally as triacylglycerol esters and steryl esters, in lipid droplets. These function primarily as anhydrous reservoirs for the efficient storage of caloric reserves and as caches of fatty acid and sterol components that are needed for membrane biogenesis. Second, the matrix of cellular membranes is formed by polar lipids, which consist of a hydrophobic and a hydrophilic portion. The propensity of the hydrophobic moieties to selfassociate (entropically driven by water), and the tendency of the hydrophilic moieties to interact with aqueous environments and with each other, is the physical basis of the spontaneous formation of membranes. This fundamental principle of amphipathic lipids is a chemical property that enabled the first cells to segregate their internal constituents from the external environment. This same principle is recapitulated within the cell to produce discrete organelles.

Lipid Regulation of the ABCB1 and ABCG2 Multidrug Transporters

“…In biological membranes, in contrast to unsaturated glycerophospholipids, SMs in the outer plasma membrane leaflet in many cases have stretched conformations, and this SM conformation allows more intimate contacts with cholesterol. Also, the larger headgroup of SM may shield the hydrophobic part of cholesterol from water; thus, SM and cholesterol may become closely packed in a partially ordered phase (Ohvo-Rekila, Ramstedt, Leppimaki, & Slotte, 2002;van Meer, Voelker, & Feigenson, 2008). The definition of such lipid rafts is quite variable and sometimes controversial (Mayor & Rao, 2004;Munro, 2003;Simons & Gerl, 2010)-biochemists and cell biologists have somewhat different approaches in this regard.…”

“…3) (Chan et al, 2013;Chawla et al, 2001;Handschin & Meyer, 2005;Jonker et al, 2009;Ory, 2004;Urquhart, Tirona, & Kim, 2007). Professional lipid ABC transporters, such as the cholesterol and phospholipid transporter ABCA1, the long-chain PC and cholesterol transporter ABCB4 (MDR3), the bile salt transporter ABCB11 (BSEP/S-P-gp), or the major sterol transporters ABCG5/G8 (working as an obligate heterodimer), have indeed been shown to be regulated by lipid-sensing NRs (Beyea et al, 2007;Jonker et al, 2009;Schmitz & Langmann, 2005;Tarling et al, 2013;van Meer et al, 2008). Interestingly, to date, several NRs also involved in the recognition of lipid ligands have been shown to affect the gene expression of human ABCB1 and ABCG2, the transport functions of which are mainly involved in causing multidrug resistance (Borst & Elferink, 2002;Jonker et al, 2009;Klaassen & Aleksunes, 2010;Natarajan, Xie, Baer, & Ross, 2012;Sarkadi et al, 2006;Scotto, 2003).…”

The phospholipid code: a key component of dying cell recognition, tumor progression and host–microbe interactions

“…The presence of nonspecific lipid transporters at the endoplasmic reticulum is thought to maintain equal distribution of phospholipids on both the luminal and cytosolic surface. 133 In contrast, phospholipid asymmetry at the plasma membrane, with phosphatidylserine (PS) and phosphatidylethanolamine (PE) found mainly at the inner leaflet, is regulated by a number of lipid transporters including P-type ATPases and ABC transporters 134 (for further discussion, see below). In addition to controlling the absolute levels and distribution of phospholipids, the availability of certain phospholipids can simply be masked by the binding of phospholipidbinding proteins.…”

Low pH Enhances the Action of Maximin H5 against Staphylococcus aureus and Helps Mediate Lysylated Phosphatidylglycerol-Induced Resistance

“…aureus, which typically contains circa 55 % PG, 40 % Lys-PG and 5 % CL at neutral pH 14, 15, 5 24 . In general, anionic lipids constitute over 80 % of the total lipid found in the membranes of Gram-positive bacteria but less than 30 % of the total lipid present in those of Gram-negative bacteria 15 .…”