Molecular "Hats" Allow in vivo Activation of Disguised Signaling Peptides

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Newswise When someone you know is wearing an unfamiliar hat, you might not recognize them. Georgia Institute of Technology researchers are using just such a disguise to sneak biomaterials containing peptide signaling molecules into living animals.

When the disguised peptides are needed to launch biological processes, the researchers shine ultraviolet light onto the molecules through the skin, causing the hat structures to come off. That allows cells and other molecules to recognize and interact with the peptides on the surface of the material.

This light-activated triggering technique has been demonstrated in animal models, and if it can be made to work in humans, it could help provide more precise timing for processes essential to regenerative medicine, cancer treatment, immunology, stem cell growth, and a range of other areas. The research represents the first time biological signals presented on biomaterials have been activated by light through the skin of a living animal, and could provide a broader platform technology for launching and controlling biological processes in living animals.

Many biological processes involve complex cascades of reactions in which the timing must be very tightly controlled, said Andrs Garca, a Regents Professor in the George W. Woodruff School of Mechanical Engineering at Georgia Tech and principal investigator for the project. Until now, we havent had control over the sequence of events in the response to implanted materials. But with this technique, we can deliver a drug or particle with its signal in the off position, then use light to turn the signal on precisely when needed.

Supported by the National Science Foundation and the National Institutes of Health, the research is reported in the December issue of the journal Nature Materials. It resulted from collaboration between scientists from Georgia Tech and the Max-Planck Institute in Germany through the Materials World Network Program.

When biomaterials are introduced into the body, they normally stimulate an immune system response immediately. But the researchers used molecular cages like hats to cover binding sites on the peptides that are normally recognized by cell receptors, preventing recognition by the animals cells. The cages were designed to detach and reveal the peptides when they encounter specific wavelengths of light.

During the five-year project, the research team which included Ted Lee and Jose Garcia from Georgia Tech and Aranzazu del Campo from Max-Planck modified peptides that normally trigger cell adhesion to present the molecular cage in order to disguise them. They showed that disguised peptides introduced into animal models on biomaterials could trigger cell adhesion, inflammation, fibrous encapsulation, and vascularization responses when activated by light. They also showed that the location and timing of activation could be controlled inside the animal by simply shining light through the skin.

The work involved numerous controls to ensure that the triggering observed by the researchers was actually done by exposure of the peptides not the light, or the removal of the protective cage. The researchers also had to demonstrate that the hats were stable enough that they didnt come off spontaneously, but only when the link between the molecular cage and the peptide was severed by the ultraviolet light.

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Molecular "Hats" Allow in vivo Activation of Disguised Signaling Peptides

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