Molecular structure of the lecithin ripple phase

Abstract

Molecular dynamics simulations of lecithin lipid bilayers in water as they are cooled from the liquid crystalline phase show the spontaneous formation of rippled bilayers. The ripple consists of two domains of different length and orientation, connected by a kink. The organization of the lipids in one domain of the ripple is found to be that of a splayed gel; in the other domain the lipids are gel-like and fully interdigitated. In the concave part of the kink region between the domains the lipids are disordered. The results are consistent with the experimental information available and provide an atomic-level model that may be tested by further experiments. molecular dynamics simulation ͉ structural model L ipid bilayers are studied widely as models for biological membranes (1). Biological membranes have many components. The complexity of the biological membrane facilitates a wide range of functionalities. Among these, order-disorder transitions within the lipid matrix are believed to play a crucial role in the regulation of protein function (2). Single-component phosphatidylcholine (lecithin) lipid aggregates in water, however, already show rich phase behavior (3). Upon cooling lecithin bilayers from the liquid crystalline (L ␣ ) state to a temperature below the main transition temperature, x-ray studies have revealed the formation of rippled bilayers (4-8). This phase is denoted P ␤ Ј. Upon further cooling below the pretransition temperature, a gel phase is found in which the lipid tails are fully stretched and ordered in a hexagonal array, with a uniform tilt with respect to the bilayer normal. This phase is denoted L ␤ Ј. X-ray studies of the P ␤ Ј phase have been used to obtain the ripple length ( r ), the stacking repeat distance (d), and the oblique angle (␥), as shown in Fig. 1 (5). The ripple is asymmetric (sawtooth-like) and consists of a major domain (M domain) and a minor domain (m domain) (6), connected by a kink. Several theories have been developed to explain the appearance of this kink. These theories either emphasize the packing frustration caused by the difference in steric requirements between the head groups and the tails of the lipids or emphasize the interaction between neighboring bilayers (for reviews, see refs. 5 and 9). Because the ripple phase is intermediate between the fluid and gel phases, study of its properties contributes to our understanding of the balance of forces within the lipid matrix and the resulting molecular organization. These insights are likely to be relevant to order-disorder transitions in a wider sense.The organization of the lipids in the domains of the ripple is unknown (10). It is generally agreed that the thickness of the lipid layer differs in the two domains (6). From x-ray scattering data the thickness of the bilayer in the M domain is found to be comparable to that found in the L ␤ Ј phase. The thickness of the bilayer in the m domain is found to be considerably smaller. It is consistent with the thickness found in the L ␣ phase, but there is no clear evid...

Biological and synthetic membranes: What can be learned from a coarse-grained description?

“…These simulations provide valuable information about the molecular organization and dynamics of the lipids and of the water, both in the bilayer and at the hydrophobic/hydrophilic interface [ 106,107,108,109]. For example, recent atomistic simulations revealed the molecular structure of the ripple phase in phosphatidylcholine bilayers [ 110]. However, calculation of these basic properties (e.g., free energy differences between different morphologies) still pose challenges to computer simulations because of the large time scales which are introduced by the interactions between head groups due to charge pairing or water bridging.…”

Mesoscopic models of biological membranes

“…De Vries et al [155] were the first to report observations of the formation of a ripple phase using atomistic MD simulations. Their results on lecithin bilayers show that packing competition between the head groups and the tails leads to the formation of the ripple phase, which shows a sawtooth shape for bilayers containing more than 128 lipids and a peristaltic shape similar to the one observed by Kranenburg et al for smaller systems.…”

“…With such a simulation one can observe the self-assembly of a vesicle [42]. However, for a systematic study that requires, for example, simulations at various temperatures, each of say 100 ns, one has to use much smaller systems, of typically 256 lipids and 10,000 water molecules [155]; this number of molecules would correspond to a bilayer patch with an area of the order of 700Å 2 . If we compare these length and time scales with the experimental systems, the limitations of MD simulations on atomistic models become evident.…”

Toy amphiphiles on the computer: What can we learn from generic models?

“…[4] On the other hand, a similar structure has recently been observed in an atomistic simulation of lecithin bilayers. [112] Our coarse-grained simulations indicate that this structure is generic, lipids do not need to have special properties to produce it. In particular, they do not need to be chiral.…”