A newly developed biomimetic system using a DNA-laced hydrogel can receive a chemical signal and release the appropriate protein, report Penn State researchers. Furthermore, continued stimulation by the chemical signal continues to trigger a response.

A hydrogel is a network of polymer chains that attract water and can be used to simulate biological tissue. Many systems in cells and in the human body are set up with a signal and response pathway. One of the best known is that of glucose, a small sugar that triggers the release of insulin.

“We’ve only done this recently in a petri dish. We did tests using smooth muscle cells, but we would of course like to do this in a living animal,"

said Yong Wang, professor of biomedical engineering.

Infused With DNA

The hydrogel, made of polyethylene glycol, is infused with two different types of DNA.

One is an aptamer — a short strand of DNA that attaches to the chemical the researchers want to release into the cell. In the case of glucose and insulin, the aptamer would bind with insulin the “drug” the researchers want to release.

The other type is a double-stranded helical molecule of DNA chosen to react with the metabolite signal — glucose — and initiate the chemical release.

[caption id=“attachment_92807” align=“aligncenter” width=“680”]DNA displacement and hybridization reactions (a) Schematic illustration of regulating the DNA-bound and free states of protein via sequential DNA displacement and hybridization reactions.
TM: triggering small molecule; AA: aptamer sequence binding to TM (e.g., adenosine used herein as a model chemical); TS: triggering DNA sequence; AP: aptamer sequence binding to a target protein (e.g., PDGF-BB).
(b) Secondary structures of aptamers of adenosine (left) and PDGF-BB (right).
Credit: Jinping Lai, et al. CC-BY[/caption]

When the signalling molecule reaches a double strand of DNA, the DNA separates into two strands. One strand binds with the molecule and the other moves toward the aptamer and forces it to release the protein bound to it.

The protein can then move through the cells to its normal binding site and perform its normal actions.

Not A Simple Process

The hydrogel system could serve as a platform for controlling the output of signalling proteins for various potential applications like drug delivery, cell regulation, molecular sensing and regenerative medicine, note the paper’s authors.

“This was not a simple process to create,” said Wang. “One graduate student worked on it for three years before giving up. In total, it took four to five years to get this far."

The researchers used adenosine as the signalling chemical and platelet-derived growth factor as the signalling protein to be released. The system can repeat the sequence, releasing signalling proteins until there are no more to release.

“We don’t yet know how to easily replenish the proteins,” said Wang.

The researchers tested the adenosine-PDGF-BB hydrogel system and found that without a signal chemical, the amount of signalling protein released by the hydrogel was very small. When the signal chemical — adenosine — was applied, the hydrogel released about 28 percent of the target signaling protein — PDGF-BB.

Other chemicals similar to adenosine, like guanosine and uridine did not cause the release of PDGF-BB from the hydrogel.

The research was supported in part by the U.S. NSF CAREER program, and the National Heart, Lung, and Blood Institute of the NIH.

Jinping Lai, et al. Displacement and hybridization reactions in aptamer-functionalized hydrogels for biomimetic protein release and signal transduction Chem. Sci., 2017, 8, 7306-7311

Top Image: Xin Zou/Jinping Lai, Penn State.

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