Scientists have developed a new way to deliver important sugar molecules directly into living cells without relying on potentially harmful organic solvents.
The technique could make it easier to study how sugars influence health and disease and may eventually help scientists modify the surfaces of cells for new purposes.
Sugars in biology are far more than sources of energy. Complex sugar molecules known as glycans cover the surfaces of cells and play important roles in communication, recognition and interactions with viruses, bacteria and other pathogens.
Changes in these sugars are also associated with diseases including cancer.
Despite their importance, glycans can be surprisingly difficult to study.
One major problem is getting them inside cells. Many sugar molecules are highly attracted to water, or hydrophilic. Cell membranes, however, contain a fatty barrier that prevents many water-loving molecules from passing through easily.
Scientists therefore often chemically modify sugars by attaching water-repelling groups that help them cross cell membranes. Preparing and delivering these modified sugars can also require organic solvents such as dimethyl sulfoxide, or DMSO, which can be harmful to cells at certain concentrations.
Professor Matthew Gibson and his colleagues have now demonstrated another approach. Their method uses a tiny boron-based structure known as a superchaotropic nanostructure to help transport sugar molecules directly into mammalian cells.
The study was published in Angewandte Chemie International Edition.
The researchers tested the approach using a technique called metabolic oligosaccharide engineering. In this method, scientists give cells specially designed sugars containing a small chemical “handle.” Once inside the cell, these sugars enter normal biological processes and eventually become incorporated into glycans.
Scientists can then use the chemical handle to track the sugars, study what they are doing or attach other molecules to them.
Using their boron-based delivery system, the researchers successfully transported unnatural sugars into cells without the usual organic solvents. The cells then processed the sugars and incorporated them into molecules displayed on their surfaces.
This effectively allowed researchers to “edit” the chemistry of the cell surface. In the future, such chemical handles could potentially be used to give cells new properties or change how they interact with their surroundings.
The researchers also applied the technique to glycoRNA, a recently discovered class of molecules in which glycans are associated with RNA. GlycoRNA has attracted considerable scientific interest, but researchers are still working to understand what these unusual molecules do inside the body.
Beyond glycan research, the new delivery method could have applications in areas such as cell engineering, infection biology, cryobiology and autophagy, the process cells use to recycle damaged or unnecessary components.
An important advantage is its simplicity. Rather than extensively modifying sugars just to help them cross cell membranes, researchers may be able to use the boron-based carrier to deliver them more directly while avoiding organic solvents.
The technology is still being developed. The team now plans to increase the amount of sugar that can be transported into cells so that the method can compete with existing techniques.
If successful, this tiny molecular delivery system could give scientists a cleaner and more flexible way to explore the complex world of sugars inside living cells.
