Imaging ionic tides and soft surfaces.

Imaging ionic tides and soft surfaces

Cellular membranes abound with ionic flows. Minibursts of sodium, potassium and other ions rush in and out of the cell as tiny channels open and close. This frenzied activity plays a key role in such things as neural impulses and muscle-fiber contractions.

A new tool -- the scanning ion-conductance microscope (SICM) -- should help biologists witness this surface activity in greater detail, say its designers. "It can image soft nonconductors such as cell membranes without touching them, and it can image ion fluxes through pores in the membranes," says codeveloper Paul K. Hansma of the University of California, Santa Barbara.

Like the scanning tunneling microscope, the SICM builds up an image of a sample surface by scanning a sharply tipped probe just above the surface's tiny hills and valleys. A feedback system raises and lowers the probe to maintain a constant electric current between the probe and the surface. Then a computer reconstructs an image from all of the probe's tiny displacements.

Electrons carry current in the scanning tunneling microscope, a device limited to imaging nonliving samples. Ions make up the current in the SICM, which "is designed specifically for biology and electrophysiology," the researchers say.

The SICM probe is a hollow glass microelectrode filled with a conductive salt solution. The researchers lower the probe toward the sample surface, which is covered in the same solution. By applying a voltage across the probe and another electrode in the sample solution, they generate a current of ions that travels through the probe. But as the probe gets very near the surface, space for ionic movement gets scarce and conductance decreases. In a scanning mode, the feedback system adjusts the probe height to maintain a constant current, creating a topographic map. For imaging local ion currents, the probe scans at a constant height and monitors the changing currents.

"Clever physiologists" might use it for making topographic maps of cell membranes and measuring the distribution and behavior of ion channels, says Hansma, who with colleagues describes the SICM in the Feb. 3 SCIENCE.

So far, the SICM researchers have successfully imaged the surfaces of acetate film and a synthetic, pore-ridden membrane filter. "It's a new way of looking at the microscopic world," says Kumar Wickramasinghe, a physicist at the IBM Thomas J. Watson Research Center in Yorktown Heights, N.Y. But he and Hansma agree that refinements in the existing device must come before its use for sophisticated membrane and ion-channel studies.