Lipids cellular membrane structure

Rouser G, Yamamoto A. Kiitchevsky G. Cellular membranes. Structure and regulation of lipid class composition species differences, changes with age and variations in some pathological states. Arch Intern Med 1971 127 1105-1121. 

Biological membranes provide the essential barrier between cells and the organelles of which cells are composed. Cellular membranes are complicated extensive biomolecular sheetlike structures, mostly fonned by lipid molecules held together by cooperative nonco-valent interactions. A membrane is not a static structure, but rather a complex dynamical two-dimensional liquid crystalline fluid mosaic of oriented proteins and lipids. A number of experimental approaches can be used to investigate and characterize biological membranes. However, the complexity of membranes is such that experimental data remain very difficult to interpret at the microscopic level. In recent years, computational studies of membranes based on detailed atomic models, as summarized in Chapter 21, have greatly increased the ability to interpret experimental data, yielding a much-improved picture of the structure and dynamics of lipid bilayers and the relationship of those properties to membrane function [21]. 

We shall mainly discuss the membranes present in eukaryotic cells, although many of the principles described also apply to the membranes of prokaryotes. The various cellular membranes have different compositions, as reflected in the ratio of protein to lipid (Figure 41-1). This is not surprising, given their divergent functions. Membranes are asymmetric sheet-like enclosed structures with distinct inner and outer surfaces. 

Our data on both disappearance of a reactant (O2 consumption) and the formation of a product (lipid-derived radical) clearly support the conclusion that cellular oxidizability increases exponentially with MBI. This exponential relationship of cellular oxidizability and polyunsaturation could be due to the close packing of unsaturated lipids in the structured environment of the membrane. 

Membrane conformational changes are observed on exposure to anesthetics, further supporting the importance of physical interactions that lead to perturbation of membrane macromolecules. For example, exposure of membranes to clinically relevant concentrations of anesthetics causes membranes to expand beyond a critical volume (critical volume hypothesis) associated with normal cellular function. Additionally, membrane structure becomes disorganized, so that the insertion of anesthetic molecules into the lipid membrane causes an increase in the mobility of the fatty acid chains in the phospholipid bilayer (membrane fluidization theory) or prevent the interconversion of membrane lipids from a gel to a liquid form, a process that is assumed necessary for normal neuronal function (lateral phase separation hypothesis). 

Cholesterol is an important structural component of cellular membranes, where it plays a role in modulating membrane fluidity and phase transitions, and, together with sphingomyelin, forms lipid rafts or caveolae, which are sites where proteins involved in diverse signaling pathways become concentrated. Furthermore, cholesterol is a precursor of oxysterols, steroid hormones, and bile acids. 

The outcome of oxidative stress is a depletion of cellular GSH, NADPH, NADH, and ATP, and also damage to lipid membranes, structural and enzymatic proteins, and DNA. 

In this chapter we first describe the composition of cellular membranes and their chemical architecture— the molecular structures that underlie their biological functions. Next, we consider the remarkable dynamic features of membranes, in which lipids and proteins move relative to each other. Cell adhesion, endocytosis, and the membrane fusion accompanying neurotransmitter secretion illustrate the dynamic role of membrane proteins. We then turn to the protein-mediated passage of solutes across membranes via transporters and ion channels. In later chapters we discuss the role of membranes in signal transduction (Chapters 12 and 23), energy transduction (Chapter 19), lipid synthesis (Chapter 21), and protein synthesis (Chapter 27). 

The glycosphingolipids of mammals are known to be cellular-membrane components,1"5 organized in such a way that their lipid moiety, namely, acylated sphingosine (usually called ceramide), is submerged into the outer leaflet of the plasma-membrane bilayer, and contributes to its structural... 

Application of an electric field to lipid bilayers such as those found in cellular membranes causes short-term depolarization of the membrane and formation of pores and other structural changes [17]. These so-called electropores allow the uptake of hydrophilic macromolecules such as plasmid DNA, siRNA, or proteins that are otherwise unable to diffuse passively through this highly regulated barrier. The use of high-voltage electrical pulses to permeabilize cell membranes was first described as a tool to deliver DNA into mammalian cells in 1982 (Wong and Neumann 1982 Neumann et al. 1982). In cuvette-based methods, cells are... 

For example, the use of a conically shaped lipid, dioleoylphos-phatidylethanolamine (DOPE), in cationic liposomes helps the destabilization of the cellular membranes, leading to a more efficient delivery of plasmid DNA in cell culture.84 The structural diversity of the lipidic colloids offers great flexibility in their applications as drug delivery and drug targeting systems. 

Lipids have several important functions in animal cells, which include serving as structural components of membranes and as a stored source of metabolic fuel (Griner et al., 1993). Eukaryotic cell membranes are composed of a complex array of proteins, phospholipids, sphingolipids, and cholesterol. The relative proportions and fatty acid composition of these components dictate the physical properties of membranes, such as fluidity, surface potential, microdomain structure, and permeability. This in turn regulates the localization and activity of membrane-associated proteins. Assembly of membranes necessitates the coordinate synthesis and catabolism of phospholipids, sterols, and sphingolipids to create the unique properties of a given cellular membrane. This must be an extremely complex process that requires coordination of multiple biosynthetic and degradative enzymes and lipid transport activities. 

Phospholipids the major structural lipids of most of our cellular membranes. 

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