Turning on cells with magnetic switches

Harvard scientists have figured out how to turn cells on and off using magnets, an advance with potentially broad applications as researchers around the world work to find new ways to manipulate cells and correct cellular functions that diseases send awry.

Donald Ingber, the Judah Folkman Professor of Vascular Biology at Harvard Medical School and Harvard-affiliated Children’s Hospital Boston, led a team that attached tiny particles with magnetic properties to cellular receptors. When exposed to a magnetic field, the particles activated the receptors to switch on the cells.

The advance, reported online in the journal Nature Biotechnology, also included Professor Mara Prentiss in Harvard’s Department of Physics. Ingber, the paper’s senior author, said it not only represents an advance in biotechnology but illustrates the value of scholars working across departments and disciplines.

The work harnesses a normal feature of cells, which have long molecules that stick out from the cell interior, passing through the cell membrane and out the other side. The outer ends of these form receptors, which bind to different things in the cell’s environment and cause the cell to switch on and off critical functions, including growth, contractility, and movement. Many receptors, such as those used in this work, do not activate the cell unless they bind molecules that link to multiple receptors simultaneously, and cause them to aggregate together in large signaling clusters.

While bioengineers can already stimulate rapid dynamic responses in nerve and muscle cells with electricity, they have continued to seek ways of exerting similar control over most of the body’s cells that don’t respond to an electrical pulse and instead respond more slowly to hormones and other soluble chemicals. The magnetic work is an approach that Ingber said may have certain advantages if it can be applied to all cells, because magnetic fields operate across barriers, such as skin, without needing wires.

“This is an example of how the boundary between living and nonliving is starting to break down,” said Ingber, who is co-chair of the Harvard Institute for Biologically Inspired Engineering. “It represents a totally different way to intersect with biology.”

The work builds on past research Ingber has done using magnetic fields to influence cellular actions. In this research, Ingber and colleagues used 30-nanometer beads on the same size scale as individual receptors with the key property that they become magnetic only when exposed to magnetic fields.

The researchers coated the beads with a molecule that binds receptors on the immune system’s mast cells. When a mast cell is activated, calcium flows inside the cells, beginning a cellular process that leads to the release of histamine, which causes inflammation around an infection site or during an allergic reaction.

After creating beads that would each bond to just one receptor, the scientists flooded the cells with the beads, ensuring that multiple receptors on each cell were bound to beads. Then, using an electromagnetic needle, they brought a magnetic field near the beads, causing them to become magnetic. Each bead behaved like a nanometer-sized bar magnet and attracted surrounding beads,
pulling the beads and attached receptors together, thereby activating the cell.

When the cells were turned on, they released calcium inside the cell membrane, starting a chain reaction that results in histamine release. When researchers moved the magnetic field away, the calcium activity stopped.

Though this research was conducted on mast cells, Ingber said there are many different cell types that are turned on through a similar type of receptor clustering that this technique could be used on.

“It really is the beginning of a new organic-inorganic interface,” Ingber said. “It’s a dynamic, controllable interface that someday might be used to directly link living cells to machines or computers.”