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Access Type

WSU Access

Date of Award

January 2020

Degree Type


Degree Name



Chemical Engineering and Materials Science

First Advisor

Jeffrey Potoff


The researches performed in this dissertation is aimed to solve the role of calcium in the membrane fusion process at the atomic level by performing molecular dynamics simulations. Membrane fusion is a mechanism of material transfer between membrane separated compartments in a cell, and one of the fundamental biological processes occurring in events, such as neurotransmission, protein transfers, and intracellular communication. It is a multi-stage and controlled mechanism, where several proteins and various factors play a role, but the details of the process have not been resolved yet. One of those several factors is the role of calcium, and their interactions with the phosphatidylserine lipids. The experimental studies showed that the extensive fusion occurs in the presence of calcium and phosphatidylserine lipids are in the composition of lipid vesicles. Since the calcium and phosphatidylserine lipid bilayer interactions can overcome the energy barriers of fusion, and the details of the interactions have not been fully studied yet, the details of the mechanism are studied in three projects.

First, the differences of bilayer physical and electrostatic properties of phosphatidylserine lipid bilayers with calcium from other systems are analyzed. The comparison showed that the bilayer physical properties are affected by the calcium attachment, but the main difference is in the additional layer of high electron density cations on the head group region. Since the head group region determines the interactions of bilayer with the other molecules, the additional calcium layer can modify these interactions. The results of orientation of water molecules and the change in the hydrogen bonding numbers of the hydration water in the close vicinity showed that the calcium can screen the interactions of head groups with the other molecules. This screening increases the number of free water molecules and the range of bulk-like water region around the bilayers. In order to analyze the screening effect of calcium on the phosphatidylserine head groups, the potential of a mean force is calculated with the adaptive biasing force method. Well known hydration repulsion phenomena prevent the merge of apposed bilayers. The removal of water molecules under the influence of head groups between the bilayers requires an increasing amount of energy with decreasing distance between the bilayers. The results of potential of a mean force showed that the calcium can screen this energy barrier between the phosphatidylserine head groups until very close contact where the apposed head groups can start the initial contact, which is salt bridge.

After bringing two bilayers into close contact, there is an energy barrier to form the early defects between the bilayers, such as salt bridges, but it occurs in the phosphatidylserine bilayers with calcium. In order to analyze the difference of this system, the energy cost of pulling a lipid from bilayer is calculated by adaptive biasing force method. This desorption free energy of a lipid is also important for the other biological activities such as lipid exchange between bilayers, and lipid flip-flop between leaflets. The results showed that the energy cost of pulling phosphatidylserine lipid from bilayer is lower with the calcium.

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