Rippled phase

Whereas the main challenge for the first bilayer simulations has been to obtain stable bilayers with properties (e.g., densities) which compare well with experiments, more and more complex problems can be tackled nowadays. For example, lipid bilayers were set up and compared in different phases (the fluid, the gel, the ripple phase) [67,68,76,81]. The formation of large pores and the structure of water in these water channels have been studied [80,81], and the forces acting on lipids which are pulled out of a membrane have been measured [82]. The bilayer systems themselves are also becoming more complex. Bilayers made of complicated amphiphiles such as unsaturated lipids have been considered [83,84]. The effect of adding cholesterol has been investigated [85,86]. An increasing number of studies are concerned with the important complex of hpid/protein interactions [87-89] and, in particular, with the structure of ion channels [90-92]. 

Lipid assemblies of the lamellar type, such as lipid bilayers, can feature a true phase transition in which the topology does not change. Upon cooling, the bilayer goes from the fluid phase to the gel phase. In the fluid phase, the acyl chains are disordered, in the sense that there is enough free volume around the chains to allow for chain conformation variations. In the gel phase, the acyl chains are more densely packed and believed to be ordered in an all-trans (straight) configuration. For very pure systems, at temperatures below this sharp gel-to-liquid phase transition, there are several other states and distinct transitions detectable (pre-transition, ripple phase, etc.). These phases will not be reviewed here. In biomembranes, many type of lipids (and other molecules) occur, and it is known that for this reason the gel-to-liquid phase transition is... 

The extensive studies of the behavior of mixed monolayers or bilayers of di-acetylenic lipids and other amphiphiles parallel to some degree the studies of dienoyl-substituted amphiphiles. Since the dienoyl lipids do not contain a rigid diacetylenic group in the middle of the hydrophobic chains, they tend to be miscible with other lipids over a wide range of temperatures and compositions. In order to decrease the lipid miscibility of certain dienoyl amphiphiles, Ringsdorf and coworkers utilized the well-known insolubility of hydrocarbons and fluorocarbons. Thus two amphiphiles were prepared, one with hydrocarbon chains and the other with fluorocarbon chains, in order to reduce their ability to mix with one another in the bilayer. Of course it is necessary to demonstrate that the lipids form a mixed lipid bilayer rather than independent structures. Elbert et al. used freeze fracture electron microscopy to demonstrate that a molar mixture of 95% DM PC and 5% of a fluorinated amphiphile formed phase-separated mixed bilayers [39]. Electron micrographs showed extensive regions of the ripple phase (Pb phase) of the DM PC and occasional smooth patches that were attributed to the fluorinated lipid. In some instances it is possible to... 

Another example worth mentioning is X-ray diffraction studies on amiodarone [80, 81], a drug that accumulates extensively in membranes (see Section 4.4). The effect of cholesterol on membrane structure has also been studied by X-ray diffraction. The results indicated the existence of microdomains in the DPPC-cholesterol mixed ripple phase [82]. 

In solutions of water and surfactant, the surfactant monolayers can join, tail side against tail side, to form bilayers, which form lamellar liquid crystals whose bilayers are planar and are arrayed periodically in the direction normal to the bilayer surface. The bilayer thickens upon addition of oil, and the distance between bilayers can be changed by adding salts or other solutes. In the oil-free case, the hydrocarbon tails can be fluidlike (La) lamellar liquid crystal or can be solidlike (Lp) lamellar liquid crystal. There also occurs another phase, Pp, called the modulated or rippled phase, in which the bilayer thickness varies chaotically in place of the lamellae. Assuming lamellar liquid crystalline symmetry, Goldstein and Leibler [19] have constructed a Hamiltonian in which (1) the intrabilayer energy is calculated... 

Sun WJ, Tristram-Nagle S, Suter RM, Nagle JF. Stmcture of the ripple phase in lecithin bilayers. Proc. Natl. Acad. Sci. U.S.A. 1996 93 7008-7012. 

A remarkable property of lipid bilayers is their structural phase transitions (thermotropic polymorphism). For example, fully hydrated pure diacyl-phosphatidyl cholines exibit one fluid phase. La and three crystalline phases Pp/, Lp/. and Lc (12). Because of the high degree of disorder caused by defects, the Pp/ and Lp/ phases usually are called gel phases. The Pp/ phase is sometimes called a ripple phase, because the surface of the bilayer is rippled (13) and presents a wave-like appearance in electron micrographs (Fig. 2). Depending on the nature of the lipid and the presence of additional components (cholesterol etc.), the Pp/ phase may be present or absent in the phase diagram, and a tilted gel Lp/ could be replaced by the Lp phase, which has similar physical properties but no tilt of the hydrocarbon chains. 

A. Ripple phase formation in phosphatidylcholine Effect of acyl 39. chain relative length, position, and unsaturation. Phys. Rev. E 1998 58 3662-3672. 

Fig. 9. Temperature-composition isobaric phase diagram for the fully hydrated dipal-mitoylphosphatidylcholine/dipalmitoyl-phosphatidylethanolamine system constructed using the temperature gradient method. The notation used is that of Luzzati [8] and is as follows Lc, lamellar crystalline (also referred to as the subgel phase) L f, lamellar gel phase with hydrocarbon chains tilted with respect to the bilayer normal P)el, ripple phase L. lamellar liquid crystal phase. Insert bold line in graph as indicated...

The lamellar phase is particularly important because, as mentioned above, it represents more or less the structure of cell membranes under equilibrium conditions. It should be added now that the name lamellar phase is not fully accurate because there are at least five lamellar phases, namely the subgel or crystalline phase, the gel or solid phase, the rippled phase, the fluid or liquid-crystalline phase, and the liquid-ordered phase. Lipids in the subgel and in the gel lamellar phase (sometimes denoted... 

The rippled phase may, upon further absorption of heat, become a liquid-crystalline phase. This phase transition is called the phospholipid main transition because of its large change in Cr as compared with the other transitions in the same system. It occurs at = 41 °C in DPPC, and AH is in this case 36 kJ/mol. See Table 4.1 for the and AH values of other lipids. The liquid-crystalline, or fluid, or bquid-disordeied phase is thought to represent the state in which most membrane lipids exist. 

The model reproduces the most prominent phase transitions of phospholipid monolayers [78] and bilayers [80]. In particular, it reproduces a main transitirm from a fluid membrane phase (L to a tilted gel phase Lpi) with an intermediate ripple phase Pp ), in agreement with experiments. The elastic parameters have been studied in the fluid phase and are in reasonable agreement with those of saturated DPPC (dipalmitoyl-phosphatidylcholine) bilayers. Recently, the Lenz model has been supplemented with a simple cholesterol model [81]. Cholesterol molecules are taken to be shorter and stiffer than lipids, and they have a slight affinity to lipids. Mixtures of lipids and cholesterol were found to develop nanoscale raft domains... 

The simple theory put forward by Meinhardt et al. accounts in a unified manner for both ripple phases and raft states in membranes. The prerequisites for the formation of such modulated phases is local phase separation (e.g., in the ripple case, between a liquid and a gel phase, or in the raft case, between a liquid disordered and a liquid ordered phase) and curvature stress in at least one of the two phases (typically the ordered one), resulting, e.g., from a size mismatch between head group and tails. In order to reproduce rippled states or rafts, coarsegrained simulation models must meet these criteria. This is often not the case. For example, the standard version of the popular MARTINI model does not have a ripple phase, because the low-temperature gel phase of saturated phospholipids is until ted. 

Lenz O, Schmid F (2007) Structure of symmetric and asymmetric ripple phases in lipid... 

Katsaras J, Tristram-Nagle S, Liu Y, Headrick RL, Fontes E, Mason PC, Nagle JF (2000) Clarification of the ripple phase of lecithin bilayers using fully hydrated, aligned samples. Phys Rev E 61 5668... 

Sengupta K, Raghunathan VA, Katsaras J (2003) Structure of the ripple phase of phospholipid multibilayers. Phys Rev E 68(3) 031710... 

Sun X, Gezelter JD (2008) Dipolar ordering in the ripple phases of molecular-scale models of lipid membranes. J Phys Chem B 112 1968-1975... 

Qualitatively similar results were obtained by Cohen and Hornreich [ 125]. In addition, it was claimed that the presence of a pretilt in the planar cholesteric texture decreases the tendency of the system to undergo transition to a periodically modulated (ripple) phase. 

Ripple phase A thermotropic phase observed in Hpid bilayers in which the membrane exhibits an out-of-plane rippled configuration. 

T is the main transition temperature corresponding to the change from the gel phase to the fluid phase,. T is the pretransition corresponding to the change from tRe tilted ordered phase to the ordered rippled phase... 

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