A new study can explore a new class of protein material that interacts with living cells without being absorbed. The material does this by binding and capturing cell surface receptors.
This discovery could have a major impact on stem cell research and enable the development of new products designed to alter the behavior of living systems.
The research, which was reported in the January 6 edition of Nature, led by the Baker laboratory at the University of Washington School of Medicine and the Derivery laboratory at the Molecular Biology Medical Research Council laboratory in Cambridge, UK The title of their paper is, Material Design 2D Bioactive Binary Protein.
Cells interact with their environment through receptors at their surface. These receptors can bind to hormones, neurotransmitters, drugs, and toxins. When such molecules bind to receptors, this triggers a response within the cell, a process called signaling.
But for the cell, it is important that this response be immobilized, in order to still respond to the signal later. To achieve this, cells typically terminate signals by absorbing both the activated receptor and the molecule that stimulated it, thus targeting both for destruction within the cell .
“This tendency of cells to enter receptors appears to reduce the efficacy of immunotherapies,” said Emmanuel Derivery, assistant professor in the MRC laboratory on Molecular Biology. “In fact, when antibody drugs bind to their target receptors and then enter and contaminate, more antibodies must always be ingested.”
To create a way around this, postdoctoral student Baker lab Ariel Ben-Sasson designed new proteins that come together in large, flat patches. This molecular scaffolding was further engineered to incorporate signaling molecules.
A graduate student of Joseph Watson of Derivery Laboratory showed that these protein products can enter cells, activate surface receptors, and resist being trapped by the cell for hours or even days.
“This work paves the way towards synthetic cell biology, where a new generation of multi-protein products can be designed to control the complex behavior of cells,” said David Baker, senior professor of biochemistry at UW School of Medicine and director of the UW Institute of Medicine for Protein Design.
By changing out which cell surface receptors the patch was targeting, the researchers showed that different cell types could be activated.
“We now have a device that can interact with any type of cell in a very specific way,” Ben-Sasson said. “This is what is exciting about protein engineering: it opens up fields that people wouldn’t expect.”
According to co-author Hannele Ruohola-Baker, professor of biochemistry at UW School of Medicine and associate director of the UW Institute of Medicine for Stem Cell and Regenerative Medicine, versions of these new products could help physicians to reduce the risks of sepsis by controlling the inflammatory response to disease.
They may even enable completely new ways to treat COVID-19, heart disease, and diabetes, and possibly reduce the effects of downstream stroke, into Alzheimer’s disease.
“This breakdown will help pave the way for the use of synthetic cell biology in regenerative medicine,” Ruohola-Baker said.
###
This press release was written by Ian Haydon of the UW Institute of Medicine for Protein Design.
Full high resolution video and youtube link
Creator: Ariel Ben-Sasson, UW Medicine
Title: 2D binary protein collection animation
Self-assembly is a process in which the same molecules, or building blocks, interact to form complex materials. This animation shows an even more complex process – assembly – where materials are assembled from a combination of two different building blocks. For material engineers and biologists looking for new equipment this development will allow control of where, when, or under what conditions the material would accumulate and the emerging buildings. Jan’s paper. 6, 2021 in Nature shows that bioengineers can form horizontal arrays rooted to the surface of a cell, stimulating and stimulating biological activity through the accumulation and inhibition of receptors ( endocytosis block). This experiment demonstrates the broad potential of this new class of design materials to close the gap between synthetic and living systems. This video was produced using Python and the Pymol (Schrödinger) graphical interface.
Disclaimer: AAAS and EurekAlert! they are not responsible for the accuracy of press releases posted to EurekAlert! by sending institutions or for using any information through the EurekAlert system.