Molecular simulations of lipid systems: Edge stability and structure in pure and mixed bilayers Público

Abstract

Understanding the structural, mechanical and dynamical properties of lipid self-assembled systems is fundamental to understand the behavior of the cell membrane. This thesis has investigated the equilibrium properties of lipid systems with edge defects through various molecular simulation techniques. The overall goal of this study is to understand the free energy terms of the edges and to develop efficient methods to sample equilibrium distributions of mixed-lipid systems. In the first main part of my thesis, an atomistic molecular model is used to study lipid ribbon which has two edges on both sides. Details of the edge structures, such as area per lipid and tail torsional statistics are presented. Line tension, calculated from pressure tensor in MD simulation has good agreement with result from other sources. To further investigate edge properties on a longer timescale and larger length scale, we have applied a coarse-grained forcefield on mixed lipid systems and try to interpret the edge fluctuations in terms of free energy parameters such as line tension and bending modulus. We have identified two regimes with quite different edge behavior: a high line tension regime and a low line tension regime. The last part of this thesis focuses on a hybrid Molecular dynamics and Configurational-bias Monte Carlo (MCMD) simulation method in which molecules can change their type by growing and shrinking the terminal acyl united carbon atoms. A two-step extension of the MCMD method has been developed to allow for a larger difference in the components' tail lengths. Results agreed well with previous one-step mutation results for a mixture with a length difference of four carbons. The current method can efficiently sample mixtures with a length difference of eight carbons, with a small portion of lipids of intermediate tail length. Preliminary results are obtained for "bicelle"-type (DMPC/DHPC) ribbons.

Table of Contents

TABLE OF CONTENTS Abstract List of Figures List of Tables Acknowledgments Chapter 1: Introduction.................................................................................................... 1 Chapter 2: Atomistic Simulation of lipid Bilayer edge................................................. 15        Introduction.................................................................................................... 16                 Methods.......................................................................................................... 19                 Results............................................................................................................ 25                         Migration of headgroups........................................................................ 25                         General morphology of the bilayer......................................................... 26                         Tail conformational statistics.................................................................. 30                         Line tension............................................................................................ 34                         Equilibrium dynamics............................................................................. 36                 Discussion....................................................................................................... 39                 Conclusion...................................................................................................... 44          Chapter 3: Coarse-grained MD simulation of mixed bilayer systems: Understanding the in-plane fluctuation of bilayer edge...................................................... 55        Introduction.................................................................................................... 56                  Methods......................................................................................................... 59                  Theory of bilayer edge shape fluctuation...................................................... 64                  A Monte Carlo model to simulate bilayer edge fluctuation.......................... 69                  Results........................................................................................................... 70                         Equilibirum dynamics............................................................................. 71                         Line tension............................................................................................ 71                         Partitioning of the short-tail lipids.......................................................... 76                         Edge contour length............................................................................... 76                         Position correlation function fourier transform...................................... 78                  Discussion...................................................................................................... 82                  Conclusions................................................................................................... 86 Chapter 4: Two-step hybrid Configurational-bias Monte Carlo and Molecular dynamics simulations of mixed lipid bilayer................................................................................................... 92        Introduction.................................................................................................... 93        Methods.......................................................................................................... 96        Results.......................................................................................................... 108                       Verification of two-step method............................................................ 108                       Simulations on DMPC/DHPC ribbon systems....................................... 109        Discussions................................................................................................... 120        Conclusions.................................................................................................. 123         

About this Dissertation

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School	Laney Graduate School
Department	Chemistry
Degree	PhD
Submission	Dissertation
Language	English
Research Field	Chemistry, Physical
Palabra Clave	lipid bilayer edge mixed-lipid systems configurational-bias Monte Carlo bicelles molecular dynamics simulation
Committee Chair / Thesis Advisor	Kindt, James, Emory University
Committee Members	Lian, Tim, Emory University Bowman, Joel M, Emory University

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