To test this technique, Groves first focused on T cells. Vital to the immune system, T cells recognize bits of antigen—any foreign material—displayed on the outer membrane of other cells. The T cell receptors (TCRs) that stud T cells bind to the antigens, which are displayed on molecules called major histocompatibility complexes (MHCs). This attachment triggers a major rearrangement of molecules, creating clusters of TCRs in bulls-eye patterns—what's known as an immunological synapse. The antigen-bearing MHCs rearrange on their cell surface as well. After a cascade of additional events occurs, the immune system is in defense mode.

Groves wanted to know what would happen if he blocked the rearrangement of TCRs. Would there still be signaling between the TCRs and MHCs? Would the MHCs still move? The spatial mutation's debut experiment answered no to both questions. When TCRs were confined to small areas of membrane, they could cluster locally within their individual corrals, but the full pattern of the immunological synapse could not form. The work, published in 2005, showed that the large-scale pattern of the immunological synapse affects signaling; in fact, it is part of the process of shutting off the signal.

More recently, Groves applied spatial mutations to cancer biology. There was already a suspicion that function and organization were linked in a protein called EphA2, a receptor that is pivotal in a cascade of signaling normally involved in cell migration; when the signaling is misregulated, it can lead to breast cancer.

Right away, when Groves's team watched EphA2 function on a synthetic membrane, they observed that it moved long distances after binding its ligand, ephrin-A1. This movement triggered reorganization of the cell's cytoskeleton. In tumor cells, the EphA2–ephrin-A1 complexes self-assemble into especially large clusters containing thousands of the proteins. So the scientists asked their standard question: what would happen if that movement was blocked?

They divided EphA2 into their gridded membrane before introducing a cell displaying ephrin-A1 proteins. Though the EphA2 could bind to ephrin-A1, the proteins couldn't cluster and the cell no longer rearranged its cytoskeleton. The results appeared in the March 12, 2010, issue of Science. Next, Groves wants to see small-molecule drugs tested on the system to learn what compounds mimic this disruption of EphA2 movement. Stopping the protein from forming clusters may block its cancer-causing ability, he says.

Groves thinks biology is full of other undiscovered examples of spatial organization affecting protein function. He says the technology of spatial mutations is well developed at this point, and he wants to keep expanding its applications. "If you look at a sentence, the information isn't in the number of letters of each type, it's in the order of those letters," he says. "The question in biology is: to what extent is information encoded in spatial arrangement rather than chemical content? I think it is, and to a large extent."

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