Investigators at Children’s Hospital Boston, in collaboration with physicists at Harvard University, developed nanobeads, particles only 30 nanometers in diameter, that, once attached to receptor molecules on the surface of a cell, were able to stimulate intracellular processes by “sensing” an external magnetic field.
When exposed to a magnetic field, the beads themselves become magnets, and pull together through magnetic attraction. This pull drags the cell’s receptors into large clusters, mimicking what happens when drugs or other molecules bind to them. This clustering, in turn, activates the receptors, triggering a cascade of biochemical signals that influence different cell functions.
The technology could lead to non-invasive ways of controlling drug release or physiologic processes such as heart rhythms and muscle contractions, says Ingber, the study’s senior investigator.
In a demonstration involving mast cells (a kind of cell in the immune system), Ingber and Mannix [Don Ingber, MD, PhD, and Robert Mannix, PhD, of program in Vascular Biology at Children’s Hospital Boston –ed.]showed that the beads, when bound to cell receptors and exposed to a magnetic field, were able to stimulate an influx of calcium into the cells. (Calcium influx is a fundamental signal used by nerve cells to initiate nerve conduction, by heart and muscle cells to stimulate contractions and by other cells for secretion.) Magnetic fields alone, without the beads, had no effect.
The beads–30-nm size (with an inner 5-nm particle) provides the optimal crystal geometry to make them “superparamagnetic”–able to be magnetized and demagnetized over and over, notes Mannix, who shares first authorship of the paper with Sanjay Kumar, MD, PhD of Children’s. (Kumar is now a faculty member in Bioengineering at the University of California at Berkeley.) To give a sense of scale, one nanometer is to a meter (about a yard) as one blueberry is to the diameter of the Earth.
The beads were made to attach to the mast-cell receptors by pre-coating them with antigens; these antigens then bound to antibodies that coated the receptors, similar to the way antibodies bind to antigens in the immune system. “Our goal was to have one antigen coating each bead, so that each bead would bind to just one receptor,” Mannix says.