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New protein patch to help scientists manipulate cell signaling

The diagram shows a new kind of protein patch attaching to the outside of a cell, which may open new treatment avenues for a range of conditions and diseases. Photo by Ian Haydon/UW Medicine Institute for Protein Design
The diagram shows a new kind of protein patch attaching to the outside of a cell, which may open new treatment avenues for a range of conditions and diseases. Photo by Ian Haydon/UW Medicine Institute for Protein Design

Jan. 6 (UPI) -- Scientists have developed a new kind of protein patch that can influence cell signaling, attaching to the outside of cells without becoming absorbed.

The breakthrough material, described Wednesday in the journal Nature, could be used to design technologies that can manipulate the behavior of biological systems.

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The new patch works by commandeering many of the receptors found on the outside of cells, which allow cells to sense and communicate with the surrounding environment.

Receptors can receive and bind with all kinds of molecules, including hormones, neurotransmitters, drugs, toxins and more. Once docked, molecules provide receptors a chemical signature, triggering reactions inside the cell -- a process called signaling.

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Because a cell's receptors are a finite resource, cells must ensure their eyes and ears to the outside world remain unclogged and unshielded -- always ready to receive new signals.

To remain undistracted, cells often absorb a recently triggered receptor and its bound molecule. Once inside the cell, the pair is destroyed.

"This tendency of cells to internalize receptors likely lowers the efficiency of immunotherapies," study co-author Emmanuel Derivery said in a news release.

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"Indeed, when antibody drugs bind their target receptors and then become internalized and degraded, more antibody must always be injected," said Derivery, assistant professor at the MRC Laboratory of Molecular Biology in Britain.

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As a workaround, researchers developed proteins that organize themselves into large, flat patches.

Next, Derivery and his colleagues embedded signaling molecules into the protein patches. When the patches attached to cells, they commandeered multiple receptors and avoided absorption for long periods of time.

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"This work paves the way towards a synthetic cell biology, where a new generation of multi-protein materials can be designed to control the complex behavior of cells," said David Baker, professor of biochemistry at the University of Washington's School of Medicine.

Researchers were able to tweak their protein patches to target different types of cell receptors.

"We now have a tool that can interact with any type of cells in a very specific way," said Ariel Ben-Sasson, the postdoctoral scholar responsible for the design of the new protein patch. "This is what is exciting about protein engineering: it opens fields that people may not expect."

Scientists plan to use the new protein patch material to mediate problematic physiological responses. For example, the patch could be used to quiet the inflammatory response to infection, preventing sepsis.

The protein patch could also eventually be used to develop new therapies for COVID-19, heart disease, diabetes and even neurodegenerative diseases like Alzheimer's, researchers said.

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