


Access Type

WSU Access

Date of Award


Degree Type


Degree Name



Chemical Engineering and Materials Science

First Advisor

Jeffrey J. Potoff

Second Advisor

Charles W. Manke


This project is focused on understanding the role of calcium in membrane fusion at the atomic level. Membrane fusion is an intense area of experimental research,

however, direct imaging of the membrane fusion mechanism has not been possible due to transient nature of the

fusion process. As an alternative to experiments, molecular dynamics simulations provide a means to investigate the structure

and function of complex biological systems, such as fusion of bilayers with atomic-scale resolution.

Nearly 40 years ago, experiments suggested pure phospholipid vesicles may undergo fusion in the presence of Ca2+.

These experiments have shown that Ca2+ interacts strongly with apposed bilayers, inducing fusion and

forming 1:2 complexes of Ca2+/PS. From these results, it was hypothesized that Ca2+

might induce fusion by reducing the electrostatic repulsion between apposed lipid bilayers. Furthermore, it

was proposed that in the initial stages of the fusion process, Ca2+ formed bridges between apposed lipid bilayers,

creating an ``anhydrous-complex'', expelling water from the lipid head groups.

The formation of the anhydrous complex and expulsion of water from the lipid head groups could lead to bilayer destabilization and eventual fusion.

In an effort to understand the role of Ca2+ in fusion of lipid vesicles, molecular

dynamics simulations have been performed on closely apposed lipid bilayers composed of DMPC and POPS in the presence of Ca2+.

Of particular interest is the formation of the hypothesized anhydrous complex between apposed phospholipids and Ca2+, and the

effect of Ca2+ on the hydration and structure of closely apposed lipid bilayers.

Molecular dynamics simulations show that

Ca2+ is capable of bridging apposed bilayers.

The bridging brings regions of the bilayers into close contact of ∼ 3 Å.

This separation is in close agreement with our preliminary simulation with DMP- in the presence of Ca2+, as well as

earlier experimental work. The process of Ca2+ bridging of apposed lipids results

in significant ordering of the lipid tails and bilayer thinning, consistent with simulations of bilayer dehydration,

validating our hypothesis that Ca2+ bridging leads to local dehydration of lipid membranes. Similar calculations

performed with Na+ instead of Ca2+ did not exhibit bridging of apposed lipid headgroups, illustrating the unique

role of Ca2+.

The simulations presented in this work provide the first evidence from atomistic simulations of the

formation of the anhydrous complex hypothesized by experiments.