X-Message-Number: 16122
Date: Tue, 24 Apr 2001 19:25:46 -0700
From: Jeff Davis <>
Subject: liposomal transmembrane cryoprotectant delivery 

The following article comes from EurekAlert at:

http://www.eurekalert.org/releases/unc-kmo042301.html

    Key mechanics of cell membrane fusion revealed 

    CHAPEL HILL - Scientists at the University of North Carolina School of
Medicine in Chapel Hill have
    developed a new working model of cell membrane fusion.

    The model, which apparently mimics the biochemical machinery of fusion
in mammalian nerve membranes, offers researchers guidance for studying the
biophysics of a process fundamental to all life. 

    In the future, knowledge gained from this research may also be applied
to human disease control. It could help enhance development of
fusion-blocking agents aimed at preventing infection by HIV, influenza,
Ebola and other viruses. These viruses use membrane fusion machinery to
enter cells. A report of the study appears in the April 10 issue of the
journal Biochemistry. It details how a group of lipids, including
cholesterol, can be combined in optimal ratios so that membrane fusion can
occur experimentally.
    Within living cells other than bacteria are compartments that carry out
different functions such as protein production and processing. And those
compartments are surrounded by a lipid bilayer membrane. Fusion allows
movement from one compartment to another.

    "The question of concern was how does the mix of lipids in a membrane
make it more or less able to fuse with another membrane," said the study's
lead author Barry R. Lentz, PhD, professor of biochemistry and biophysics
at UNC. 
    Lentz, who heads UNC's Program in Molecular and Cellular Biophysics,
and his collaborators approached the question by looking at a highly
"fusagenic" membrane, one that's central to nervous system functioning: the
synaptic vesicle membrane. Synaptic vesicles fuse with the surface membrane
of the neuron, releasing neurotransmitters that bind to the adjacent neuron.
    Lentz and his colleagues have developed a fusion model for that
membrane based on liposomes, lipid sacs they produced in the laboratory
from pure lipids. The researchers found that the addition of the polymer
polyethylene glycol forced the liposomes close together and that they could
then manipulate them to make them fuse. They had already discovered that
fusion between these liposomes behaved in a remarkably similar fashion to
fusion reported by other scientists between biological membranes. 
    By mixing several pure lipids in different proportions, Lentz and Md.
Emdadul Haque, PhD, of UNC and Thomas J. McIntosh, PhD of Duke University
Medical Center found they could optimize fusion with a mix of lipids
(cholesterol, phosphatidylcholine, sphingomyelin, phosphatydilethanolamine
and phosphatidylserine) basically in the same proportions found in natural
synaptic vesicle membranes. 
    "What we found was really mind-blowing. The optimal mix that allows
membranes to fuse to the greatest extent and rupture or lose their contents
to the least extent was exactly the mix Nature has designed for the
synaptic vesicle in mammalian cells. Very little is known about how lipid
compositions affect fusion. This report offers the first insights into how
Nature has optimized membranes for fusion and should help scientists better
design liposomes for delivery of drugs into cells by fusion," Lentz said
    "This is one more piece of evidence for what I see as the predominant
hypothesis in the field now -- that fusion in a biological membrane is a
process by which lipids undergo physical changes just like they undergo in
the lab," Lentz noted. 
    But Lentz points out that lipids are not enough to drive fusion. The
chemical machine that makes those changes occur also involve proteins. "And
that's what we're studying now with our liposome model," he said.
                                     ###

    The research was supported by grants from the U.S. Public Health Service. 

    media note: Contact Dr. Lentz at 919-966-5384;  
    School of Medicine contact, Les Lang, 919-843-9687;  



			Best, Jeff Davis

	   "Everything's hard till you know how to do it."
					Ray Charles	

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