A
long-standing mystery in cell biology may be closer to a solution
thanks to measurements taken at the National Institute of Standards and
Technology (NIST) and France’s Institut Laue-Langevin (ILL), where
scientists have observed changes in the thickness of a model cell
membrane for the first time. The findings, which confirm that
long-predicted fluctuations occur in the membranes, may help biologists
understand many basic cellular functions, including how membranes form
pores.
Every
cell in your body is surrounded by a cell membrane, a thin, flexible
wall made of fatty molecules that maintains the integrity of the nucleus
and the rest of the cell’s interior. Cells need a way to take in
nutrients and expel waste across the membrane, and generally this
involves lodging special proteins in the membrane. These proteins form
holes that can open and close, acting as gateways to the interior.
Before
these proteins take their place in the membrane, they float freely
about the cell’s protoplasm. But just how the membrane—whose job, after
all, is to form an otherwise impermeable barrier—allows these proteins
to penetrate it in the first place is largely a mystery, though one clue
might lie in its dynamic nature.
“The
cell membrane is not a static barrier. It’s always moving, its
thickness fluctuating and waves rippling through it,” says Michihiro
Nagao of the NIST Center for Neutron Research (NCNR). “Some theories
indicate that if a protein is near the interior of the membrane when it
is moving in just the right way, this movement might allow the protein
to work its way in somehow.”
The
research team constructed a set of artificial membranes and analyzed
their movement with a spin echo machine, a very specialized device of
which there are only a few in the world. After a lengthy measurement
effort, the team eventually found that when warmed to around body
temperature, the membrane thickness fluctuated by up to 8 percent
roughly every 100 nanoseconds, or 30 times slower than for comparable
nonbiological sheets.
“Some
theories indicate that some form of motion like this must be happening
for pores to form, so it’s exciting to actually see them,” says Paul
Butler, also of the NCNR.
It
will take time to understand completely the cause of the fluctuations,
why they are so slow, and how they enable protein insertion, but Butler
points out that knowledge of the speed and size of the fluctuations will
be helpful in designing therapies to control dysfunction in membrane
permeability, including the creation of undesirable pores that lead to
cell death.
“This
research gives us a tool with which we can measure the effect of
potential therapeutic agents on the thickness fluctuations,” Butler
adds.
The operation of the instrument at NIST is funded in part by the National Science Foundation.
Lipid bilayers and membrane dynamics: Insight into thickness fluctuations
Source: NIST