Elucidating lipid conformations in the ripple phase Machine learning reveals four lipid populations

A new mixed radial-angular, three-particle correlation function method in combination with unsupervised machine learning was applied to examine the emergence of the ripple phase in dipalmitoylphosphatidylcholine (DPPC) lipid bilayers using data from atomistic molecular dynamics simulations of system sizes ranging from 128 to 4096 lipids. Based on the acyl tail con-formations, the analysis revealed the presence of four distinct conformational populations of lipids in the ripple phases of the DPPC lipid bilayers. The expected gel-like (ordered; L-o) and fluid-like (disordered; L-d) lipids are found along with their splayed tail equivalents (L-o,L-s and L-d,L-s). These lipids differ, based on their gauche distribution and tail packing. The disordered (L-d) and disordered-splayed (L-d,L-s) lipids spatially cluster in the ripple in the groove side, that is, in an asymmetric manner across the bilayer leaflets. The ripple phase does not contain large numbers of Ld lipids; instead they only exist on the interface of the groove side of the undulation. The bulk of the groove side is a complex coexistence of L-o, L-o,L-s, and L-d,L-s lipids. The convex side of the undulation contains predominantly Lo lipids. Thus, the structure of the ripple phase is neither a simple coexistence of ordered and disordered lipids nor a coexistence of ordered interdigitating gel-like (L-o) and ordered-splayed (L-o,L-s) lipids, but instead a coexistence of an ordered phase and a complex mixed phase. Principal component analysis further confirmed the ex-istence of the four lipid groups.

Automated summary

A new method combining mixed radial-angular, three-particle correlation function and unsupervised machine learning was used to investigate the emergence of the ripple phase in DPPC lipid bilayers. Data from atomistic molecular dynamics simulations of varying system sizes were analyzed, revealing four distinct conformational populations of lipids. The presence of ordered, disordered, and splayed tail lipids was observed, with spatial clustering of disordered lipids in the groove side of the ripple phase. Principal component analysis confirmed the existence of the four lipid groups.