- Email: [email protected]
Probing the immune response with nanotechnology
RESEARCH NEWS
Toucan play at the strength game MECHANICAL PROPERTIES
The structure of a toucan beak (left) and the interior foam structure (right) constructed from a fibrous protein network. (© 2005 Elsevier.)
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
Probing the immune response with nanotechnology NANOTECHNOLOGY 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 cellcell junction, surrounded by a ring of adhesion molecules. This complex assembly is known as the
16
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
JAN-FEB 2006 | VOLUME 9 | NUMBER 1-2
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
Toucan play at the strength game MECHANICAL PROPERTIES
The structure of a toucan beak (left) and the interior foam structure (right) constructed from a fibrous protein network. (© 2005 Elsevier.)
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
Probing the immune response with nanotechnology NANOTECHNOLOGY 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 cellcell junction, surrounded by a ring of adhesion molecules. This complex assembly is known as the
16
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
JAN-FEB 2006 | VOLUME 9 | NUMBER 1-2
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