The molecular face of lipid rafts in model membranes

Herre Jelger Risselada, ‪Siewert J. Marrink

Proceedings of the National Academy of Sciences · 2008 · 552 citations · 31 references

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TL;DR

Cell membranes are composed of diverse lipid species, and their multicomponent mixtures exhibit complex phase behavior with structural and compositional heterogeneity, particularly in ternary mixtures of saturated and unsaturated lipids with cholesterol that resemble raft‑like domains. The study applies a simulation model to assess the nanoscale molecular nature of raft‑like domains, a detail previously inaccessible experimentally. The simulation model analyzes a saturated phosphatidylcholine/unsaturated PC/cholesterol mixture to reveal liquid‑ordered and liquid‑disordered phases. The simulations show spontaneous separation into liquid‑ordered and liquid‑disordered phases that match experimental data, reveal detailed domain and interface structures, predict a small surface tension driving leaflet registration, and suggest a surprising molecular face of raft‑like mixtures with implications for cell membrane processes.

Abstract

Cell membranes contain a large number of different lipid species. Such a multicomponent mixture exhibits a complex phase behavior with regions of structural and compositional heterogeneity. Especially domains formed in ternary mixtures, composed of saturated and unsaturated lipids together with cholesterol, have received a lot of attention as they may resemble raft formation in real cells. Here we apply a simulation model to assess the molecular nature of these domains at the nanoscale, information that has thus far eluded experimental determination. We are able to show the spontaneous separation of a saturated phosphatidylcholine (PC)/unsaturated PC/cholesterol mixture into a liquid-ordered and a liquid-disordered phase with structural and dynamic properties closely matching experimental data. The near-atomic resolution of the simulations reveals remarkable features of both domains and the boundary domain interface. Furthermore, we predict the existence of a small surface tension between the monolayer leaflets that drives registration of the domains. At the level of molecular detail, raft-like lipid mixtures show a surprising face with possible implications for many cell membrane processes.

References

31