Jay Groves is a chemist who holds appointments with Berkeley Lab, UC Berkeley and HHMI. (Photo by Roy Kaltschmidt, Berkeley Lab) |
Football
has often been called “a game of inches,” but biology is a game of
nanometers, where spatial differences of only a few nanometers can
determine the fate of a cell—whether it lives or dies, remains normal or
turns cancerous. Scientists with the U.S. Department of Energy (DOE)’s
Lawrence Berkeley National Laboratory (Berkeley Lab) have developed a
new and better way to study the impact of spatial patterns on living
cells.
Berkeley
Lab chemist Jay Groves led a study in which artificial membranes made
up of a fluid bilayer of lipid molecules were embedded with fixed arrays
of gold nanoparticles to control the spacing of proteins and other
cellular molecules placed on the membranes. This provided the
researchers with an unprecedented opportunity to study how the spatial
patterns of chemical and physical properties on membrane surfaces
influence the behavior of cells.
“The
gold nanoparticles are similar to the size of a single protein
molecule, which gets us to a scale we couldn’t really access before,”
says Groves. “As the first example of a biological membrane platform
that combines fixed nanopatterning with the mobility of fluid lipid
bilayers, our technique represents an important improvement over
previous patterning methods.”
Groves
holds joint appointments with Berkeley Lab’s Physical Biosciences
Division and the University of California (UC) Berkeley’s Chemistry
Department, and is a Howard Hughes Medical Institute (HHMI)
investigator. He is the corresponding author of a paper that reports
these results in the journal Nano Letters. The paper is titled “Supported Membranes Embedded with Fixed Arrays of Gold Nanoparticles.”
Schematic shows gold nanoparticle arrays embedded into a supported lipid bilayer membrane then selectively labeled with specific surface chemistry properties to study living cells that are bound to the nanoparticles and/or lipid bilayer. (Groves, et. al) |
Spatial
patterning of chemical and physical properties on artificial membranes
of lipid bilayers is a time-tested way to study the behavior of cultured
biological cells. Natural lipid bilayer membranes surround virtually
all living cells as well as many of the structures inside the cell
including the nucleus. These membranes provide a barrier that restrains
the movement of proteins and other cellular molecules, penning them into
their proper locations and preventing them from moving into areas where
they do not belong. Past spatial patterning efforts on artificial
membranes have been done on an all-or-nothing basis—proteins placed on a
membrane either had complete mobility or were fixed in a static
position.
“Immobile
patterning intrinsically defeats any cellular process that naturally
involves movement,” Groves says. “On the other hand we need to be able
to impose some fixed barriers in order to manipulate membranes in really
novel ways.”
Groves
is a recognized leader in the development of unique “supported”
synthetic membranes that are constructed out of lipids and assembled
onto a substrate of solid silica. He and his group have used these
supported membranes to demonstrate that living cells not only interact
with their environment through chemical signals but also through
physical force.
“We
call our approach the spatial mutation strategy because molecules in a
cell can be spatially re-arranged without altering the cell in any other
way,” he says.
However,
until now Groves and his group were unable to get to the tens of
nanometers length-scales that they can now reach by embedding their
supported membranes with gold nanoparticles.
“Our
new membranes provide a hybrid interface consisting of mobile and
immobile components with controlled geometry,” Groves says. “Proteins or
other cellular molecules can be associated with the fluid lipid
component, the fixed nanoparticle component, or both.”
Gold nanoparticles in a lipid membrane can be coupled to biomolecules for the study of specific cellular functions. Here gold nanoparticles have been coupled to biotin (vitamin B7), which plays an essential role in cell growth. (Groves, et. al) |
The
gold nanoparticle arrays were patterned through a self-assembly process
that provides controllable spacing between particles in the array in
the important range of 50 to 150 nm. The gold nanoparticles
themselves measure about five to seven nanometers in diameter.
Groves
and his team successfully tested their hybrid membranes on a line of
breast cancer cells known as MDA-MB-231 that is highly invasive. With
their hybrid membranes, the team demonstrated that in the absence of
cell adhesion molecules, the membrane remained essentially free of the
cancer cells, but when both the nanoparticles and the lipid were
functionalized with molecules that promote cell adhesion, the cancer
cells were found all over the surface.
Groves
and his research group are now using their gold nanoparticle membranes
to study both cancer metastasis and T cell immunology. They expect to
report their results soon.
Co-authoring the Nano Letters
paper with Groves were Theobald Lohmuller, Sara Triffo, Geoff
O’Donoghue, Qian Xu and Michael Coyle. This research was supported by
the DOE Office of Science.
Supported Membranes Embedded with Fixed Arrays of Gold Nanoparticles