aerogels research aids cell membranes

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Stanford News: Aerogels May Spawn Life-Like Lab-on-a-Chip Devices and

Better Model Membranes

STANFORD, Calif.--(BUSINESS WIRE)--March 12, 2004--It`s the tale of the

princess and the pea, science-style. Proteins sitting on a glass

microscope slide can have a hard time getting comfortable. Atop a bed of

compact silica, they can become confined, contorted and damaged - and

may even lose their biological functions.

If the princess had had a waterbed instead of a hard mattress, she`d

never have been kept awake by the discomfort of a pea. Similarly,

embedding proteins in a lipid bilayer creates a comfy environment a lot

like the protein`s natural resting place in a cell membrane. And laying

that protein-studded lipid bilayer on a hydrated cushion may allow the

proteins to better keep their natural forms and functions.

Thanks to Stanford inventors, proteins now have their waterbed. It`s

created from a novel aerogel - a light, porous silica material that can

be formulated to be between 50 percent and 98 percent empty. When its

pores are filled with a biological buffer, the resulting substrate may

support cell membranes just as a cell body would, allowing researchers

to study functional components under life-like conditions.

The Stanford researchers have succeeded in creating lipid membranes on

the surface of extraordinarily porous liquid-filled aerogel. This

technology is now available for licensing through Stanford`s Office of

Technology Licensing. Next, the researchers hope the substrate will

allow integral membrane proteins to remain as intact and functional in

experimental systems as they are in living cells. Doing so may improve

model membranes for research and enable the creation of novel biosensors

and lab-on-a-chip devices, arrays for screening drugs that bind to

membrane-embedded receptors and libraries that display membrane proteins

in their natural shapes.

``If we`re successful in the entire construction, we`ll be able to put

proteins in an environment in which they`ll remain functional, and we

can have access to them for analytical techniques as well as provide the

proteins with any other sort of environmental conditions that are

appropriate,`` says Chemical Engineering Department Chair Curtis ,

the W. M. Keck, Sr. Professor in Engineering. recently filed a

patent for the aerogel technology with visiting Professor Subhash Risbud

from the University of California-, graduate student Weng and

postdoctoral fellow Johan Stalgren. The researchers collaborate in the

Center on Polymer Interfaces and Macromolecular Assemblies (CPIMA), a

National Science Foundation-sponsored partnership among Stanford, IBM

Almaden Research Center, UC- and UC-Berkeley.

Maintaining proteins in a physiological state is a major engineering

challenge. While engineers have made lipid bilayers stand up on compact

silicon wafers before, the Stanford invention is the first to allow

assembly of bilayers on a porous and hydrated silicon substrate. The

atomically rough, corrugated surface of the Stanford material and its

abundance of water-loving hydroxyl chemical groups make it possible for

the lipids to essentially walk on water. ``It`s sort of like having

matchsticks stand on ocean,`` Risbud says.

Membrane-bound proteins represent the single most important class of

drug targets, Weng says. Approximately 50 percent of current targets are

membrane-bound molecules. Keeping the components of these molecules

functional with supported lipid bilayer systems may improve biochemical

and biophysical studies of antibody binding, drug binding and other

interactions. Drug target screening is an important potential

application of such systems.

The CPIMA group collaborates with Assistant Professor of Medicine

and graduate student Lynn Radosevich, both of

whom study autoimmune diseases, such as multiple sclerosis. Many

membrane components, such as glycolipids and proteins, can induce

dysfunctional immune-system cells to attack. Aerogel technology may

increase the chances of membrane components behaving naturally during

experiments.

Aerogels also facilitate the production of patterned (and hydrated)

lipid bilayers useful in multiple chemical assays of biological samples.

Microarrays created with the technology may someday find use in

high-throughput assays. Patterned bilayers may also aid tissue

engineering, allowing researchers to direct cell growth to make, say, an

artificial retina.

Aerogel also allows experimenters first-time access to both sides of the

cell membrane - the outer membrane, where drugs bind to embedded

receptor proteins, as well as the inner membrane, where signals trigger

physiological events, such as neurochemical communication. Scientists

could also study the transport of substances through the membrane, such

as ions traveling through a protein channel. Compact silica glass

slides, in contrast, allow researchers access to only one side of a

membrane.

Just as a jellyfish retains its shape after it washes up on a beach and

dries, so too do aerogels retain their structure as they`re being

produced in the lab - despite the fact that they are more air than gel.

That structure is an amorphous network of small molecules - in the case

of the Stanford substance, silicon dioxide with attached organic groups.

The key to creating the Stanford aerogel is a process that allows the

gel solution to dry without shrinkage. Called supercritical drying, it

exchanges carbon dioxide with the solvent used to prepare the gel

solution. Under a scanning electron microscope, the resulting structure

resembles haphazardly interlacing strings of pearls. To the naked eye,

the macroscopic material looks like Jell-O. A dry chunk of aerogel,

translucent and fragile, feels lighter than Styrofoam.

Scientist S. Kistler made the first aerogel in 1931 and patented

it in 1937. The history is unclear about whether he accomplished this

while at Stanford or the College of the Pacific in Stockton. His first

aerogels were made of silica, but he also made aerogels of alumina,

tungsten, iron and tin oxides, nickel tartrate, cellulose, gelatin, egg

whites and rubber.

While hydrated aerogels have important biological applications, dry

aerogels show promise, too. They have been components of particle

detectors in high-energy physics. Their high porosity means their

thermal conductivity is about 100 times less than that of fully dense

silica glass, paving the way for use in superinsulating spacers in

windows and in shields to trap solar energy. As sound moves slower

through aerogels than air, they may improve efficiency of devices that

emit ultrasonic waves to gauge distances, such as auto-focusing cameras

and some robots.