Cells in humans and animals are resilient in fending off intruders, which is why so many potentially beneficial drug cures are unsuccessful during development because they can’t cross cell membranes of bacteria, viruses or cancers.
Now, Michael P. Schramm, assistant professor of chemistry at California State University, Long Beach (CSULB), along with undergraduate students Katie M. Feher and Hai Hoang, recently demonstrated that they could embed a molecule inside a vase-shaped carrier molecule called a cavitand that they created, then successfully insert it into a cell membrane. Their article, “Embedding resorcinarene cavitands in lipid vesicles,” appeared in the New Journal of Chemistry.
“Our goal in this project is to develop a synthetic receptor that could be put into a cell membrane that would selectively transport a molecule of our choosing,” Schramm said. “This is a pretty ambitious project and it’s technically challenging. There already are commercially available pharmaceutically relevant methods to transport drugs—there are special ways you can formulate a drug in terms of types of molecules that you can mix in with a drug to help it penetrate. A lot of people are working on this but we are looking at just a very simple idea of making our own receptor that would transport just the molecules that we want, introducing it to a cell-based assay and transporting our molecules across.”
Their work is funded by a three-year, $433,500 grant from the National Cancer Institute via the National Institute of General Medical Science’s Support of Competitive Research (SCORE) program.
One of the main problems confounding pharmaceutical researchers lies in the fundamental construction of cells, Schramm explained. “Every cell in our body is composed of a bilayer that’s part water loving and part fat [lipid] loving. The lipid part is like mixing oil and water, forming droplets and beads. They assemble in a very specific way so that the oil-like parts stick together and the water-like parts stay together. Lipids make up this layer that keeps the internal contents of the cell separated from the external contents. This lipid layer forms a sphere and there are important things inside and important things outside, but the two are separated.”
There already are natural molecules that cause transport in cells, Schramm continued. “There’s an antibiotic compound in nature that lodges in the cell membrane and only transports potassium ions across a cell membrane. The characteristics of this particular molecule, valinomycin, are very similar to our cavitands. They’re vase-shaped, they hold a small molecule inside and they have a preference for localizing in the cell membrane. We think those are some of the key criteria to develop this type of chemistry to manifest this idea of making a synthetic molecule to transport drugs selectively.”
The SCORE grant funding is aimed at supporting research by students and encouraging them to go into science careers. Study co-author Katie Feher will begin a chemistry Ph.D. at New York University this fall, and other undergraduate and master’s students are carrying on the research. In addition, Schramm has hired post-doctoral research associate to work on the project.
Schramm currently is studying this process using liposomes, which are lab-made sacs, or vesicles, surrounded by a membrane, and eventually will try his cavitand molecules in organism cells. The next step is getting his lab’s cavitands to release the molecules they holds into the interior of cells.