Synthetic cells

Chris Keating wants to know something basic about how cells work. "How does a given molecule within a cell get to the place where it wants to go?" she asks.

To find the answer, a great many researchers have tried taking cells apart. But Keating, an assistant professor of chemistry at Penn State, is using a different approach: she's building a cell from scratch.

Synthetic Cell

"We're trying to do something really simple," she explains. "Instead of taking things out of a cell to see when it stops working, we start with an empty cell membrane and figure out what we have to put in before it takes on the properties of a cell." ("I'm looking for functions right now, not for the whole thing to be alive," she hastens to add.)

As a first step, Keating and her team have focused on a fundamental cell characteristic called heterogeneity. "We know that molecules inside the cell are not just uniformly swimming around," she explains. "They are actually very heterogeneous. And you can explain that heterogeneity in a lot of ways, one of which could be phase separation"—as when an egg white separates from the yolk.

"People have made lipid bilayers"—the fatty membranes common to all cells—"that form giant vesicles that are the size and shape of a cell," she says. "We're saying, Okay, let's take it a step closer by putting in a model of the cytoplasm," the fluid that fills most cells.

To do that, Keating uses a combination of liquid polymers, polyethylene glycol (PEG) and Dextran. When the two are mixed together, they form a substance called an aqueous two-phase polymer system (ATPS).

Put simply, when the ATPS is mixed in a test tube coated with a dry lipid film and allowed to stand, the lipid film gets wet and forms an elliptical two molecule-thick cell vesicle that both contains and is surrounded by the single-phase ATPS solution. Adding heat causes the PEG and Dextran to separate into discrete phases. In the test tube, the heavier Dextran goes to the bottom and the PEG rises to the top. In the "cell" vesicle, the PEG collects on the inside perimeter of the vesicle wall while the Dextran collects at the center, forming a phase-separated microcompartment within the vesicle.

Although a great many physical forces are known to affect heterogeneity in complex ways, for now Keating is working with two: heat and osmotic pressure, which can be controlled by adjusting the concentration of ingredients in the solution.

"Cytoplasm has a lot of big molecules suspended in it that take up a lot of space, which results in something called volume exclusion, which means there's less space for other molecules," she notes. "That crowding changes the properties of molecules more than you would think. It has a huge impact on how they behave—for instance, whether they stick together or not.

"If you put some molecules in a beaker wandering around in water, they usually won't interact, but if you put them in a crowded place like cytoplasm, they might stick together. And they will behave differently than if they were not stuck together. This is a really important part of how cells work," she says.

As it gains in complexity, Keating's synthetic cell may hold promise for industries ranging from cosmetics and pharmaceuticals to food technology, in addition to aiding investigations in fundamental cell biology, she says.

"This is an entirely new approach to the cell model system," she says. "I'm hoping it will enable us to do lots of new things."

Christine D. Keating, Ph.D., is assistant professor of chemistry in the Eberly College of Science, and the recipient of a Young Investigator Award from the Arnold and Mabel Beckman Foundation, a CAREER Award from the National Science Foundation, and a Unilever Outstanding Young Investigator Award from the American Chemical Society. She can be reached at cmd8@psu.edu.

Last Updated September 04, 2007