C&EN: TODAY'S HEADLINES - SURFACE FREES THE OLD, BIND THE NEW

MAUREEN ROUHI

In what they call an important advance, University of Chicago chemists have prepared a surface that performs two functions: It releases a bound ligand when an electrical potential is applied and then immobilizes a new ligand in place of the old one. The researchers—Woon-Seok Yeo, Muhammad N. Yousaf, and Milan Mrksich—believe that this dynamic surface could be used to study ligand-receptor interactions between cells and the extracellular protein matrix to which cells are attached.

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DESIGNERS Yeo (left) and Mrksich with apparatus for applying electrical potentials to designed surfaces.
COURTESY OF MRKSICH LAB

The dynamic properties are evident from the adhesion of cells to a peptide that is part of the ligand. When ligands are attached to the surface, cells stick. When the ligands are disconnected, cells are released.

“We’re trying to create substrates that can be used to model the dynamic changes in extracellular matrix ligands that cells are seeing all the time,” Mrksich says. “That has just been impossible to do because methods that allow immobilized ligands to be switched on and off in the presence of cells have been lacking.

“Our electroactive substrates make a significant advance in this direction. With surfaces that selectively turn ligands on and off, it will now be possible to carry out experiments to determine how cellular activities respond to a change in immobilized ligands.”

Vincent M. Rotello, a chemistry professor at the University of Massachusetts, Amherst, says the work pushes further “the interfacing of electronics and cellular processes”; that is, “the two-way communication between the in vivo and the in silico worlds.”

The work also may have broader impact: According to Christopher Gorman, an associate chemistry professor at North Carolina State University, Raleigh, it “should get people thinking not only about how to influence cells but also about how chemically controlled dynamic surfaces could be used in other arenas, such as controlled growth of materials.”

The team uses electrochemistry to release a ligand from the surface and to later replace it. The original ligand is linked to the surface through an O-silyl hydroquinone. Also attached to the silicon atom is the peptide to which cells bind naturally. An applied potential oxidizes the hydroquinone to benzoquinone, the Si–O bond breaks, and the peptides—with the bound cells—are released. In addition, the electrochemical changes set up the chemistry for installing a new ligand.

The benzoquinone, still on the surface, can easily undergo a Diels-Alder reaction. A ligand consisting of the cell-adhesive peptide tethered to cyclopentadiene can be selectively immobilized through a cycloaddition between benzoquinone and cyclopentadiene. When the ligand is installed, cells bind to the peptide. But if the benzoquinone is electrochemically converted to the hydroquinone, no reaction occurs and no cells adhere to the surface [J. Am. Chem. Soc., 125, 14994 (2003)].

“What’s next,” Mrksich says, “is to apply the dynamic substrates to specific signaling pathways in cell biology.” Also still to be achieved is a system that can repeatedly bind and release ligands. The problem is not easy, he adds, and his group has been evaluating different chemistries for such a system.

DYNAMIC Cells are evenly distributed on a surface coated with two different cell-adhesive compounds, one of which is electroactive (left panel). An applied potential breaks the O–Si bond and releases the ligands and the cells bound to them, leaving cells adhering only to areas coated with the nonelectroactive compound (center). A Diels-Alder reaction installs a new ligand, and the surface is again evenly covered with cells.
COURTESY OF DAL-HEE MIN AND WOON-SEOK YEO