Molecular dynamics simulations of the structure and phase behaviour of model lipid membranes and the effect of hydrostatic pressure
File(s)
Author(s)
Carter, James
Type
Thesis
Abstract
Lipid membranes have a rich and complex phase behaviour, involving topological changes to the three-dimensional shape of the membrane, changes to the molecular packing within the membrane and changes to molecular conformations. Studying this phase behaviour can reveal a lot about the fundamental chemistry and physics which govern these systems and the roles that this phase behaviour might play in biological processes. In this work, molecular dynamics simulations are used to investigate the structure, properties and phase behaviour of a range of different lipid membrane systems. The widely used MARTINI model is shown to be able to reproduce the gel/fluid phase transition in single component membranes and Lo/Ld phase separation in ternary mixtures with qualitative agreement with experiment. The compositions of the Lo and Ld phases are calculated and the ternary phase diagram is plotted revealing a wide Lo/Ld coexistence region. The p-T solid/liquid phase diagram for the MARTINI water model is also calculated as a useful resource for future simulations. Non-equilibrium molecular dynamics simulations are used to show that a thermal gradient across a membrane can induce asymmetry in the cholesterol composition and flip-flop process. The effect of the thermal gradient and cholesterol asymmetry on the structure of the membrane is also investigated at steady-state. Cholesterol is found to be thermophobic, with a higher affinity for the colder membrane leaflet due to the more ordered lipid tails. The gel phases formed by different MARTINI POPC topologies are compared revealing very different structures. A new backmapping definition for the current MARTINI POPC topology is defined and used to generate an atomistic gel phase. Simulations using the slipids forcefield show that the final gel phase structure is strongly dependent on the initial configuration. Finally, methods to generate a primitive bicontinuous cubic phase and to calculate the optimum water per lipid ratio in a cubic phase are presented. The effectiveness of both methods is demonstrated by simulations using a new MARTINI topology for monoelaidin.
Version
Open Access
Date Issued
2019-09
Date Awarded
2021-06
Copyright Statement
Creative Commons Attribution NonCommercial NoDerivatives Licence
Advisor
Bresme, Fernando
Seddon, John
Brooks, Nicholas
Sponsor
Engineering and Physical Sciences Research Council (EPSRC)
Publisher Department
Chemistry
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)