Nanopatterned substrates have been used by

researchers at the University of California, Berkeley

(UCB), Lawrence Berkeley National Laboratory, and

New York University School of Medicine to give an

insight into a cell-signalling process that is vital to the

body’s immune response [Mossman et al., Science

(2005) 310, 1191].

“This marriage of inorganic nanotechnology with cells

enables us to go inside a living cell and physically

move around its signaling molecules with molecular

precision,” says Jay T. Groves of UCB.

The immune system responds to markers on the

surface of a cell called antigens. Cells presenting

foreign antigens are recognized by T cells, sparking a

biochemical signaling pathway that activates the

T cells and mounts an immune response. First, T cell

receptor (TCR) proteins recognize antigens presented

on the cell surface by the major histocompatibility

complex (MHC). Next, these TCR-MHC complexes

become organized at the center of a specialized cell-

cell junction, surrounded by a ring of adhesion

molecules. This complex assembly is known as the

immunological synapse, and it controls T cell signaling

and activation.

“Scientists, including ourselves, have posed elaborate

theories about how the strength and duration of

signals that activate T cells are controlled by

immunological synapses without having been able to

do direct experimentation,” explains Groves.

His team developed an experimental platform to

manipulate how the receptor-ligand complexes move

within the cell membrane to form the immunological

synapse, and measure what effect this has on T cell

signaling.

Lipid membranes supported on a silica substrate

provided an artificial cell surface complete with MHCs

onto which T cells were deposited. Fluorescent labels

were used to follow the subsequent formation of the

immunological synapse and initiation of T cell signaling.

By patterning the silica substrates with 100 nm wide

Cr lines using electron-beam lithography, barriers to

the movement of TCR-MHC complexes within the

supported lipid membrane were created. This changed

the spatial pattern of molecules within the

immunological synapse and altered TCR signaling.

The researchers were able to determine that the

immunological synapse is formed in three steps: MHCs

are bound by the TCRs, TCR-MHC complexes assemble

into microclusters, and the microclusters are

transported to form the center of the synapse. This

final translocation step regulates TCR signaling: if it is

prevented, signaling is switched on for longer. This is a

surprising result, showing that the duration of the

activation signal is related to the spatial organization

and transport of the T cell receptors.

“This may explain why autoimmune diseases are so

difficult to treat,” says Groves. “TCR proteins do not

respond like a conventional target, where if you hit the

bull’s eye you trigger a signal. The spatial position of

the receptor determines the type of signal it triggers.”

This experimental method should be useful for studies

of other intercellular signaling processes. Groves and

coworkers are now looking at neuronal synapse

formation and signaling mechanisms in the

development of cancer.

Jonathan Wood

Probing the immune response with nanotechnology NANOTECHNOLOGY

Toucan play at the strength game MECHANICAL PROPERTIES

A toucan’s beak makes up a third of its length

but only a twentieth of its mass, yet has

outstanding stiffness. This is because of its

optimized closed-cell foam structure, say Marc A.

Meyers and colleagues at the University of

California, San Diego [Seki et al., Acta Mater.

(2005) 53, 5281].

The beak consists of a keratin shell around a

closed-cell foam made of a fibrous network of

proteins, with a hollow center. “I did not think it

would be a foam inside the beak, and I did not

think it would be a closed-cell system,” says

Meyers. “The closed cell gives additional rigidity.

Also, the foam is Ca rich like a boney material.”

The keratin layer consists of hexagonal scales

that are 2-10 µm in thickness and 30-60 µm in

diameter. When these scales are glued together,

they exhibit tensile strengths of 50 MPa and a

Young’s modulus of 1.4 GPa.

The high Ca content of the fibers in the foam

give a Young’s modulus twice as high as in the

keratin shell. Furthermore, the combined

response of the foam and shell shows there is a

synergistic effect that gives a greater capacity to

absorb energy than the sum of the parts.

The foam structure, however, isn’t an original.

The toucan’s beak is similar to other bird beaks

and avian claws. “We have foam sandwiches, it’s

nothing new. But the toucan’s beak is more than

a sandwich structure – it is optimized. It teaches

us we can really improve on what we have [in

synthetic structures],” says Meyers.

This research returns Meyers to a hunting trip

with his father 40 years ago, where he found an

incredibly light yet strong toucan skeleton in the

Brazilian jungle.

Patrick Cain

The structure of a toucan beak (left) and the interior foam structure (right) constructed from a fibrous

protein network. (© 2005 Elsevier.)

JAN-FEB 2006 | VOLUME 9 | NUMBER 1-2 16

RESEARCH NEWS