Simulation of Lipid or Surfactant Aggregates and Membrane-Protein Interactions

Due to their amphipathic nature, surfactant and lipid molecules in an aqueous environment readily aggregate to form a wide variety of distinct phases, including the formation of micelles and lamellae, as well as hexagonal and cubic phases. The mechanical and structural properties of these different phases vary significantly depending on the chemical composition of the lipid or surfactant as well as the thermodynamic state of the system. Understanding this complex phase behaviour has important biological, as well as industrial, implications. For example, gallstone formation is believed to be initiated by the formation of micro-crystals of cholesterol within mixed micelles containing phospholipid, cholesterol and bile salts. The group is investigating a variety of systems to determine the nature of the forces that stabilise specific phases and that drive spontaneous phase changes. Work has concentrated on the spontaneous aggregation of lipids and surfactants, the thermodynamics of pore formation in bilayers and the simulation of processes such as vesicle fusion. This work is a strict test of the ability of the simulations to reproduce different aspects of the complex phase behaviour of the lipids used. The work has also allowed us to investigate, for example, the mechanism by which small vesicles form and fuse to form larger vesicles. The simulations clearly support the so-called stalk mechanism, where in the initial stages of fusion the two vesicles are bridged by a small lipid stalk that gradually grows, eventually leading to the formation of a pore.

Simulations have also demonstrated that the process of phase transformation from disordered (liquidlike) to ordered (gellike) states of lipid bilayers can be studied in molecular detail. In this way, the size and nature of nucleation seeds can be determined. The so-called ripple phase of phosphatidylcholine lipids was found to form spontaneously after cooling down a bilayer in the liquid-crystalline state at high-enough hydration. The macroscopic structure of this phase is well known but the molecular organisation within this structure is subject to debate, in particular in the thin arm of the ripple structure. As can be seen in figure 2 the simulations predict that the lipids in the thin arm of the ripple structure are ordered and interdigitated. This is in contrast to the commonly heard belief that the lipids in this part of the ripple are disordered. On the basis of the simulations, angle-resolved Wide-Angle X-ray Scattering experiments have been proposed, which should resolve the issue of the organisation of the lipids in the ripple phase.

This page was last updated on July the 10th, 2017.

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