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Scientists use molecular thinners and light shakers; chemical to build platforms for tissue engineering



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Scientists use molecular thinners and light shakers; chemical to build platforms for tissue engineering

Photographs of epidermal growth factor proteins (EGF) on one side of a human cell. Left: EGF (green) has been tied to a single human hydrogel (center). The cell membrane binds EGF, making its membrane green. Middle: The hydrogel after using a laser to undo and release EGF proteins on the upper part of the cell. Right: Image shows the difference in green fluorescent color between post-release and pre-release images. Note the increase in color in the upper part of the cell, which shows that the cell has begun to internalize the EGF proteins without tightening them but only on one side. A scale bar is 10 micrometers. Credit: Shadish, Benuska and DeForest, 2019, Nature Materials

Tissue engineering could transform medicine. Instead of waiting for our bodies to regenerate or repair damage after injury or disease, scientists could grow complex, fully functional tissues in a laboratory to transplant them to patients.


Proteins are key to this future. In our bodies, protein signals say cells where to go, when to share and what to do. In the laboratory, scientists use proteins for the same purpose – placing proteins at specific points on or within engineering scaffolding, and then using these protein signals to control cell migration, division and differentiation.

But proteins in these locations are also fragile. To get them to stick to the scaffolding, researchers have traditionally adapted proteins using pharmacies that kill more than 90 percent of their function. In a paper published May 20 in the magazine Nature Materials, a team of researchers from the University of Washington unveiled a new strategy to keep proteins complete and practical by adjusting them at a particular point so that they can be chemically tied to the scaffold using light. As the tether can also be cut by laser light, this method can create evolutionary patterns of signal proteins across biodegradable scaffolding to grow tissues containing different types of cells.

"Biological information communicators are ultimately proteins," said corresponding author Cole DeForest, a PC assistant in chemical engineering and bioengineering, as well as a link researcher with the Cell PC Institute and PC Regenerative Medicine. "They drive almost every change in cell function – discrimination, movement, growth, death."

For that reason, scientists have long used proteins to control cell growth and differentiate in tissue engineering.

Scientists use molecular thinners and light shakers; chemical to build platforms for tissue engineering

Photorelease of proteins from hydrogel. Top: The red mCherry fluorescent proteins are tied to the hydrogel. Researchers can split the tether with light to direct it (blue arrows), releasing the mCherry of the hydrogel (blue arrows). Bottom: Image of the hydrogel after a mherherry release has been battered in the shape of a University (black) mascot University of Washington. A scale bar is 100 micrometers. Credit: Shadish, Benuska and DeForest, 2019, Nature Materials.

"But the pharmacies most commonly used by the community for binding proteins into materials, including scaffolding for tissue engineering, destroy the vast majority of their function," said DeForest, who is also a faculty member at the Institute of Engineering and Molecular Sciences. PC. "Historically, researchers have tried to compensate for this by overloading the scaffold with proteins, knowing that most of them will be inactive. Here we have created a common way to activate biomaterials reversible with proteins while n keep their activity full. "

Their approach uses an enzyme of the sorting name, found in many bacteria, to add short synthetic peptide to each signal protein at a specific location: the C-terminus, a site present on all protein. The team designs that peptide of such kind as it will tie the signal protein to specific locations within liquid biodegradable scaffolding which is common in tissue engineering, known as hydrogel t .

Targeting one site on the signal protein is what sets a separate PC team approach. Other methods adjust signal proteins by attaching chemical groups to random locations, which often interfere with the function of protein. Adapting only C-terminus of the protein is much less likely to disrupt its function, according to DeForest. The team tested the approach on more than half a dozen different types of proteins. The results show that adjusting the C-terminus does not have any significant effect on protein function, and manages to spread the proteins through the hydrogel.

Their approach is like hanging a piece of art to frame on a wall. Instead of hammering random nails through the glass, canvas and frame, they are a single wire string across the back of each frame to hang on the wall.

In addition, the tether can be broken by exposure to a focused laser light, causing a "photorelease" of the proteins. The use of this scientific light saber allows the researchers to load hydrogel with many different types of protein signals, and then exposes the hydrogel to laser light to irregular proteins of certain parts of the body; hydrogel. By only disclosing extracts from the materials to the laser light selectively, the team controlled where protein signals would remain trapped to the hydrogel.

Scientists use molecular thinners and light shakers; chemical to build platforms for tissue engineering

Left to right: DeForest Cole, Gabrielle Benuska, Jared Shadish. Credit: Dennis Wise / University of Washington

Unstable proteins are useful in hydrogels as cells could then use those signals, bringing them into the inside of the cell where they can affect processes such as gene expression.

The DeForest team tested the photorelease process using a hydrogel growth factor with an epidermol, a type of protein signal. They introduced a human cell line to the hydrogel and noticed the growth factors that binded the cell membranes. The team used a laser light beam to unravel the protein signals on one side of a single cell, but not the other side. On the tie side of the cell, the proteins remained on the outside of the cell as they were still stuck to the hydrogel. On the innocent side, the protein signals were internalized by the cell.

"Based on how we target the laser light, we can ensure that different cells – or even different parts of single cells – receive different environmental signals," said DeForest.

This unique level of accuracy in a single cell not only helps with tissue engineering, but with basic research in cell biology, DeForest added. Researchers could use this platform to study how living cells respond to multiple combinations of protein signals, for example. This research line would help scientists understand how protein signals work together to control cell differentiation, improve infected tissue and promote human development.

"This platform allows us to control exactly when and where bioactive protein signals are presented to cells within materials," DeForest said. "That opens the door to many exciting applications in tissue engineering research and therapeutics."


Use biological process, hydrogel signals and release of proteins


More information:
Jared A. Shadish et al. Proteins have been customized to sites for a 4D pattern of gel materials which have been specifically customized. Nature Materials (2019). DOI: 10.1038 / s41563-019-0367-7

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University of Washington

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