Use this URL to cite or link to this record in EThOS:
Title: Computational study of electrostatic contribution to membrane dynamics
Author: Kiselev, Vladimir
ISNI:       0000 0004 2732 4718
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2011
Availability of Full Text:
Access from EThOS:
Full text unavailable from EThOS. Please try the link below.
Access from Institution:
Electrostatics plays a crucial role in the membrane biology. Negatively charged lipids (such as PS, PA and PIP2) are subject to redistribution under the action of electrostatic forces during various signalling events. Membrane recruitment of multiple signalling proteins (such as MARCKS or Src kinase) is often maintained by positively charged polybasic domains (PD). Even though adsorption of these proteins to the cellular membrane has been extensively investigated, very little is known about how electrostatic interactions contribute to their membrane lateral dynamics. This thesis presents an investigation of the contribution of electrostatic interactions to the membrane lateral dynamics by means of novel computational tools. First, I developed a dynamic Monte-Carlo automaton that faithfully simulates lateral diffusion of the adsorbed positively charged PD of a peripheral membrane protein, as well as the dynamics of mono- (PS, PA) and polyvalent (PIP2) anionic lipids within the bilayer. This model allowed to investigate the major characteristics of protein-membrane diffusion on the uniform membrane. In agreement with earlier results, the simulations revealed the following microscopic phenomena: 1) Electrostatic lipid demixing in the vicinity of the PD; 2) PD interacts with PIP2 stronger than with monovalent lipids. On the spatially heterogeneous membrane the automaton predicted a directional drift of the PD, which was validated by a simple mean-field analytical model. The predicted phenomenon could potentially play a major role in membrane domain formation. To test this hypothesis and to investigate the membrane dynamics on larger scales I developed a continuous model, which was based on the results of the automaton simulations. The results of the continuous model and the Monte-Carlo simulations were shown to be in quantitative agreement. The continuous model allows one to simulate the electrostatic membrane dynamics on micrometer scales and can be used to describe various biologically important processes, such as endocytic cup initiation.
Supervisor: Goryachev, Andrew. ; Swain, Peter. Sponsor: Darwin Trust of Edinburgh
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: acidic lipids ; electrostatic sequestration ; charged membranes ; diffusion coefficient ; adsorbed basic peptides ; membrane dynamics