Introduction: Membrane Properties (Good) for Life

Abstract

Membranes protect cells from the surrounding environment but also provide a means for the optimization of processes such as metabolism, signalling, or mitogenesis. Membrane structure and function is determined by its molecular composition. How lipid species define membrane properties is discussed in this introductory chapter.

Appendix: Lipid Phases and Acyl Chain Ordering in Model Membranes

Physical properties of membranes are important factors for cell function but due to current technical limitations cannot be studied in living cells with high precision or, in some cases, not at all. Model membranes with well-defined composition (e.g., giant unilamellar vesicles; GUVs) provide an excellent subject for biophysical studies and enable characterization of physical properties with good accuracy and reproducibility. In model membranes, lipids can form at least three phases which differ in freedom with which lipids can move around: the most rigid—solid (So), the most relaxed—liquid disordered (Ld), and somewhat intermediate—liquid ordered (Lo) phase. Phase behavior of lipids depends on the melting temperature (Tm) of lipids in a mixture and the presence of cholesterol. Temperature-gradient experiments with individual lipids and phase diagrams for bi- and ternary lipid mixtures uncovered some interesting complexities in lipid phase behavior and, especially, the importance of cholesterol (and other sterols) for the liquid character of cellular membranes [58, 59]. Cholesterol has rigidifying effect on lipids with low Tm, but it also prevents formation of solid phase by high Tm lipids. Currently, a phase diagram for 4-component lipid mixture was reported [60]. Data generated with even more complex lipid mixtures are difficult to interpret and we may wait another 5–10 years for phase diagram of 5-component mixture. In addition, no classical lipid phases can be expected in non-equilibrium system of living cells. Therefore, a more general property of lipid mixtures, lipid ordering or conformational order of acyl chains, was suggested for studies of complex lipid mixtures and cell membranes in order to better characterize the rigidity of a local membrane environment [61]. Reporters of lipid ordering have been established—fluorescent probes which can sense the presence or absence of water molecules in membranes, solvatochromic membrane dyes. Higher penetration of water molecules to the hydrophobic core indicates reduced rigidity of the membrane. To date, the best membrane order probe is probably Laurdan and its derivative, C-Laurdan (see Chapters 3 and 10; [62]). More ordered membranes can be easily distinguished from disordered parts in phase separated monolayers and GUVs [61, 63]. Since solid (or gel)-like phase is not expected to last for long in living cells, there is no problem that these probes cannot distinguish Lo from So phase. In cells, differences in lipid ordering are expected to be less pronounced due to a high complexity of lipid mixture and the presence of proteins. Indeed, data from cell-derived vesicles, GPMVs or cell-derived blebs (Chapter 6), show significant but small difference in values detected by C-Laurdan [64]. Even smaller differences are observed in living cells for intracellular membranes compared to the plasma membrane at physiological temperature [19, 65]. This indicates that organization of membranes in living cells depends more on subtle variation of local membrane composition and properties than on a large segregation of molecules due to their physical properties. It is, therefore, important to focus on a local membrane environments and changes therein. But model membranes represent an excellent tool for studies of molecules in a defined environment and adjusting our methods for future cell experiments. Cell-derived vesicles then function as a bridge between these two worlds, artificial and natural. In addition, in silico simulations provide unprecedented tool to investigate local relations before doing costly experiments (Chapters 20 and 21).