How the Membrane Got its Ripples

Phase transitions of lipid membranes have drawn a lot of attention for well over 50 years. In 1973, Tardieu, Luzzati and Reman discovered the ripple phase in their X-ray diffraction experiments of single component membranes [1]. When a bilayer consisting of large head group lipids is cooled below the main phase transition temperature, it undergoes a transition to the ripple phase consisting of sawtooth-shaped ripple on the two sides of the membrane. Furthermore, the ripple is asymmetric having a major and a minor arm. The nature and molecular structure of this phase has been intensely discussed since its discovery. The typical textbook description is that the gel and fluid phases of lipid bilayers are planar and conformationally homogeneous, but in contrast to that picture, the ripple phase undulates in an asymmetric sawtooth pattern and consists of heterogeneous conformational clusters. In this talk, I discuss the properties of the ripple phase, and molecular dynamics simulations and machine learing (ML) combined with 3-body correlation functions to resolve the molecular conformations that give rise to the ripple [2]. The ML approach developed here is also applicable to various multicomponent systems, and I will discuss some of its applications.[1] Structure and Polymorphism of the Hydrocarbon Chains of Lipids: A Study of Lecithin-Water Phases. Tardieu, A.; Luzzati, V.; Reman, F. C. J. Mol. Biol. 75, 711–733 (1973).[2] Elucidating Lipid Conformations in the Ripple Phase: Machine Learning Reveals Four Lipid Populations. Davies, M; Reyes-Figueroa, A.D.; Gurtovenko, A.A.; Frankel, D.; Karttunen, M. Biophys. J. 122, P442-450 (2023).