TY - JOUR

T1 - Elucidating lipid conformations in the ripple phase: Machine learning reveals four lipid populations

AU - Davies, Matthew

AU - Reyes-Figueroa, A.D.

AU - Гуртовенко, Андрей Алексеевич

AU - Frankel, Daniel

AU - Karttunen, Mikko

PY - 2023/1/17

Y1 - 2023/1/17

N2 - 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 conformations, 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,s and L d,s). These lipids differ, based on their gauche distribution and tail packing. The disordered (L d) and disordered-splayed (L d,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 L d 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,s, and L d,s lipids. The convex side of the undulation contains predominantly L o 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,s) lipids, but instead a coexistence of an ordered phase and a complex mixed phase. Principal component analysis further confirmed the existence of the four lipid groups.

AB - 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 conformations, 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,s and L d,s). These lipids differ, based on their gauche distribution and tail packing. The disordered (L d) and disordered-splayed (L d,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 L d 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,s, and L d,s lipids. The convex side of the undulation contains predominantly L o 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,s) lipids, but instead a coexistence of an ordered phase and a complex mixed phase. Principal component analysis further confirmed the existence of the four lipid groups.

KW - Cell Membrane

KW - Lipid Bilayers/chemistry

KW - Machine Learning

KW - Molecular Conformation

KW - Molecular Dynamics Simulation

UR - https://www.mendeley.com/catalogue/fff03382-6912-31bc-b35f-aa79dede53e8/

U2 - 10.1016/j.bpj.2022.11.024

DO - 10.1016/j.bpj.2022.11.024

M3 - Article

C2 - 36403088

VL - 122

SP - 442

EP - 450

JO - Biophysical Journal

JF - Biophysical Journal

SN - 0006-3495

IS - 2

ER -