A team of biologists believe they have created the first ever example of hydrogels inside of living cells.
Researchers from Johns Hopkins University have created the hydrogels, which if created on demand, could shed light on the role hydrogels that form in nature when proteins or other molecules aggregate under certain conditions, play on human diseases.
“The exciting part of this work is not just that we made hydrogels but that we’re now equipped with this powerful technique that lets us ask fundamental, and very challenging questions about them,” Takanari Inoue, Ph.D., an associate professor of cell biology at the Johns Hopkins University School of Medicine and senior author of the study, said in a statement.
Hydrogels are any solid gel material that holds together due to tight connections among its molecules, but also absorbs significant amounts of water.
Most floating structures are enclosed by membranes in living structures, helping them retain their shape in the cells’ watery cytoplasm.
However, when the cells undergo stress including from heat, starvation or infection, proteins and ribonucleic acid (RNA) molecules can clump into stress granules, which are free of enclosing membranes and often form small globs.
In the past, scientists have linked natural hydrogels to various neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), with too many or too few stress granules impacting the cells’ ability to function.
“These hydrogels lack membranes, so it’s hard to isolate and purify them,” Inoue said. “They’re so fragile that we can’t just collect them like we can with nuclei or mitochondria.”
The researchers designed a system they called iPOLYMER, composed of two binding proteins— FKBP and FRB— and an immunosuppressive chemical and drug called rapamycin.
To create this system, they engineered cells to contain two kinds of protein strings composed of tandem FKBPs and FRBs and then added rapamycin, which enabled them to be able to observe how the hydrogels form.
They now plan on modifying the system so that the hydrogels integrate RNA molecules into their structures, allowing them to better mimic the stress granules seen in human cells.
The researchers also plan on creating a system in which FKBP and FRB form liquid droplets so that they can compare the effects of the liquid droplet and hydrogel forms of the protein structures.
