For the first time, researchers have demonstrated a means of controlling cell functions with a physical, rather than chemical, signal. Using a magnetic field to pull together tiny beads targeted to particular cell receptors, Harvard researchers made cells take up calcium, and then stop, then take it up again. Their work is the first to prove that such a level of control over cells is possible. If the approach can be used with many cell types and cell functions, it could lead to a totally new class of therapies that rely on cells themselves to make and release drugs.

The research, which appeared in the journal Nature Nanotechnology, was led by Donald Ingber, professor of pathology at Harvard Medical School and cochair of the Harvard Institute for Biologically Inspired Engineering. Ingber's group demonstrated its method for biomagnetic control using a type of immune-system cell that mediates allergic reactions. Targeted nanoparticles with iron oxide cores were used to mimic antigens in vitro. Each is attached to a molecule that in turn can attach to a single receptor on an immune cell. When Ingber exposes cells bound with these particles to a weak magnetic field, the nanoparticles become magnetic and draw together, pulling the attached cell receptors into clusters. This causes the cells to take in calcium. (In the body, this would initiate a chain of events that leads the cells to release histamine.) When the magnetic field is turned off, the particles are no longer attracted to each other, the receptors move apart, and the influx of calcium stops.

"It's not the chemistry; it's the proximity" that activates such receptors, says Ingber.

The approach could have a far-reaching impact, as many important cell receptors are activated in a similar way and might be controlled using Ingber's method.

"In recent years, there has been a realization that physical events, not just chemical events, are important" to cell function, says Shu Chien, a bioengineer at the University of California, San Diego. Researchers have probed the effects of physical forces on cells by, for example, squishing them between plates or pulling probes across their surfaces. But none of these techniques work at as fine a level of control as Ingber's magnetic beads, which act on single biomolecules.

"Up to now, there hasn't been much control [over cells] at this scale," says Larry Nagahara, project manager in the National Cancer Institute's Alliance for Nanotechnology in Cancer and a physics professor at Arizona State University.