Occasionally, the tools built to make an experiment possible attain significance far beyond the experiment that spawned their creation.

Milan Mrksich loves pointing this out. “New directions in science are launched by new tools much more often than by new concepts,” he says, quoting the physicist Freeman Dyson. “The effect of a concept-driven revolution is to explain old things in new ways. The effect of a tool-driven revolution is to discover new things that have to be explained.”

That sentiment explains why Mrksich, an HHMI investigator at the University of Chicago, tackles questions in biology by building new tools. The revolutionary advances within modern biology are often associated with the development of a new tool, he points out. “The polymerase chain reaction, green fluorescent protein, DNA synthesis—these are the tools that allow life scientists to do their work,” he says.

Mrksich is studying the interplay between cells and the extracellular matrix of proteins that surrounds them, supports them, and guides their development. “The matrix is dynamic,” he says. “Proteases are degrading the matrix, cells are remodeling it, and growth factors and other proteins are binding to it so that they can interact with cell-surface proteins. It's very challenging to study.”

Right now, the best available way is to affix a single layer of a matrix protein of interest in a Petri dish. “Once you do that, the cells will attach, they'll spread, and one can then study the relationship between the protein layer [and] the cells,” he says. But that technique can't mimic the matrix's constant remodeling.

So Mrksich engineered a better Petri dish that can mimic the dynamic matrix by turning the signaling molecules, called ligands, on and off. The engineered surface consists of a glass slide coated with a layer of gold thin enough to be transparent. Carpeting the gold is a layer of molecules that anchor ligands. The ligands are “hidden” from cells growing on the dish by a small molecule that pops off in the presence of voltage, allowing the ligand to interact with receptors on the cell. “So we can grow cells on the layer, and then, when we want, flip a switch and turn those ligands on [or off] and see how the cell responds to the changes,” he says.

Mrksich has a history of sharing tools he developed with other labs. Eventually, he will do the same with this matrix mimic. But not yet. “We've spent a long time developing this tool. Now we're applying it to questions,” he says.

—Benjamin Lester

HHMI INVESTIGATOR