What separates living things from the inanimate world? On the most fundamental level it is a barrier of fat and protein that encloses a living cell. Until now, the simplest model of a cell that biologists have been able to create is a vesicle--a tiny balloon made up of a single layer of fat molecules, or lipids, curled into a sphere. People like these because if you put something inside you can separate it from everything on the outside, says Joseph Zasadzinski, a chemical engineer at the University of California at Santa Barbara. So you can use them as a drug delivery system and encapsulate a drug that might be toxic, then have it released only very slowly into the circulation or only at a particular site.
Vesicles are useful, says Zasadzinski, but a better drug carrier would more closely mimic real cells. That is, it would have two membranes instead of one. And it might contain several vesicles within one larger package, to allow the delivery of more than one drug at a time. Drugs carried in vesicles within vesicles would have to diffuse through both layers and would, theoretically, be released more slowly, lengthening the time between treatments. We figured that if one membrane is good, two might be better, he says. Zasadzinski and his group recently succeeded in making such a double-membraned vesicle.
It wasn’t easy. We had to figure out a nice gentle way to wrap something around something else. To create his fake cells, Zasadzinski first made conventional vesicles, each with tiny molecules called biotins embedded in its lipid membrane. To these vesicles he added a bacterial protein called streptavidin. Each streptavidin protein binds to biotin molecules on different vesicles, linking them together.
He then mixed clusters of these linked vesicles with another fatty brew made out of a molecule called phosphatidylserine. The brew contained biotin and streptavidin to make it stick to the vesicles. Zasadzinski also added calcium to the mix, which made the fatty molecules wrap around the clusters of vesicles, forming enclosed, cell-like structures.
Zasadzinski hopes that his vesicle packages will provide a way to put many different drugs into one-cell containers. Before his artificial cells can be used to deliver drugs, though, Zasadzinski will have to find a replacement for the bacterial protein used to create his vesicles--it invariably triggers an immune response in the body. There is a company that actually makes artificial biotin and streptavidin, but they haven’t given us any to try yet, Zasadzinski says. We are just getting into the realm where this might actually make some money, so everyone is reluctant to share anything anymore.
