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Artificial Cells


Researchers are learning to make designer cells for dehydrated blood supplies and space-age medicines.

by Karen Miller

Red blood cells are great at carrying oxygen. Unfortunately, that's about all they do. Let's face it: with a little bit of help, they could be a lot more useful.

Imagine, for example, blood cells that could carry all kinds of things--medication as well as oxygen. Imagine blood that could be dehydrated, and stored for months or even years at a time. It could be carried by medics onto a battlefield--or by astronauts into outer space. Imagine blood that could be used for transfusions with no risk of AIDS or any other disease.

A group of university researchers is helping NASA develop an artificial cell that can do all this and more.

Bioengineers Dan Hammer and Dennis Discher of the University of Pennsylvania and Frank Bates of the University of Minnesota have created a special kind of molecule--a polymer--that forms something very like a cell membrane, and they've been able to coax these membranes into artificial cells, or polymersomes, that are stronger and more easily manageable than the real thing.

A polymer is simply a chain of smaller molecules that have been linked together. The cellulose in plants and the wool on sheep are natural polymers. Man-made polymers can be found in everything from nylon stockings to car parts to furniture stuffing.



Credit: Iowa St. University

Red blood cells.


The polymers used in polymersomes are larger and heavier than the natural molecules in cell membranes: They've got a molecular weight of over 3600, compared to about 750 for phospholipids, the fatty acid molecules used by cells.

Manmade molecules can be crafted with an important characteristic, which many naturally occurring molecules share; they can be engineered to be amphiphilic, where one end seeks water, and the other end avoids it. In a water-based solution, such molecules spontaneously arrange themselves into a double-layer with their hydrophobic (water fearing) tails in the middle and their hydrophilic (water loving) heads on the outside.

"That was our insight," said Hammer. "We realized that there's nothing that prevents a polymer from forming a bilayer like a phospholipid would."

But polymersomes have one huge advantage: they can be controlled. By adding in different molecules, researchers are learning to manipulate their abilities and make them do things that biological cells just can't manage.

For example, polymersomes can be made strong. While it's true that the phospholipids in natural membranes hold together, they don't bond with each other very tightly. They move around within the cell membrane, and, without the pressure of a watery environment, they fall apart.



Credit: University of Pennsylvania

Giant, 2-20 mm, polymersomes in phosphate buffered saline €“ visualized by phase-contrast microscopy (internal solution of 300 mM sucrose).


Polymersomes, on the other hand, can be designed so that they cling to each other tightly. Their atoms can bond not only within a single polymer, but also to the polymers next to them. This is called cross-linking, and it vastly increases the strength of artificial cells. (It's cross-linking that stiffens the curls in a beauty-shop permanent enough to keep the shape of the hair-do.) In fact, between cross-linking and the increased molecular weight of the polymers, polymersomes are a thousand-fold stronger than phospholipid cells.

"Probably the main advantage from NASA's point of view," says Hammer, "is that once the polymersomes are crosslinked, the cells become durable enough to be dehydrated into a powder." They can be stored easily, for a long time, and without taking up much space. In other words, it would be a perfect way to carry extra blood for medical emergencies on long distance voyages in outer space.

That, in fact, is the use that he and his colleagues initially envisioned, says Hammer. But they quickly realized that the polymersomes could be used for transporting other things.

Hammer explains: It's easy to encapsulate many kinds of molecules with polymersomes; such artificial cells could then be sent throughout the body. Because their outer membrane consists of molecules that don't interact with cells, polymersomes are invisible to the immune system. They can travel unhampered through the bloodstream.

Polymersomes can also be engineered so that some types of cells do react to them. Hammer, Discher and colleagues can add to their polymersomes particular molecules that latch onto the cells they're targeting. Typically, says Hammer, the polymersomes float through the bloodstream for about 18 hours before they reach their destination and grab onto the target cells.



Credit: University of Pennsylvania

This sequence of microscopic photos shows how a tough crosslinked polymersome can be dehydrated (for, e.g., easy storage and transportation) and rehydrated again.


The key word is "target." Doctors using polymersomes wouldn't have to pepper the entire body with medications. They could be targeted--sent only to the places they're needed. Arthritis medications, for example, could be sent only to a patient's swollen fingers, without the risk of causing reactions elsewhere. Polymersomes could carry cancer-zapping pharmaceuticals directly to a tumour. They could incorporate imaging agents like iron oxide particles, which can be detected by magnetic resonance imaging. If these particles are encapsulated into polymersomes designed to latch onto cancer cells, they'd be able to locate small tumour. cells that have migrated through the body.

Polymersomes could theoretically be designed to carry both the imaging agents that locate a problem, and the medication that treats it.

Using manmade materials to produce an artificial cell is "a highly novel concept," says Hammer. "I think that NASA saw this as a wonderful material, and they wanted to see how far it could evolve." In some conditions, he says, polymersomes take on shapes that are very reminiscent of the ones biological cells take on when, for instance, they're dividing.

And Hammer and his colleagues are still exploring the possibilities. They're experimenting with different types of polymers, to see how the capabilities of artificial cells can be expanded.

The most exciting applications of polymersomes, believes Hammer, are still to come.

 

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First Science 2014