Deep within the cells we are made of, squishy skeletons feel the effects of gravity... and respond in unexpected ways.

by Karen Miller and Dr Tony Phillips

Sculptor Kenneth Snelson's "Needle Tower" is a fragile-looking thing. Criss-crossing rods suspended by taut wires soar perilously upward 20 meters high. Surely it ought to crumble or fall over? Yet it doesn't. When the wind blows, the Needle Tower bends, not breaks. When someone shoves it, it shoves back. The tower is lightweight, strong and curiously beautiful.

Just like the skeletons of cells.

That's right, cells have skeletons. They're not made of calcium like the bones that rattle on Halloween. Cell skeletons-biologists call them cytoskeletons - consisting of protein molecules arranged into chains. Cytoskeletons give cells their shape, help cells move, and hold the nucleus in place.

Like Snelson's sculptures, cytoskeletons have 'tensegrity' - short for tensional integrity. They balance compression with tension, and yield to forces without breaking. In the Needle Tower, the wires carry tension and the rods bear compression. In a cytoskeleton, protein chains - some thin, some thick and some hollow, take the place of wires and rods. Linked together they form a stable, but flexible, structure.

NASA is interested in cytoskeletons because cytoskeletons respond to gravity. Weight can provide both tension and compression. But what happens (during space travel, for example) when weight vanishes? Do cells behave differently when their cytoskeletons relax?

Harvard cell biologist Don Ingber is a leader among researchers who have been working to find out.

"The cytoskeleton perceives gravity-or any force- through special proteins known as integrins, which poke through the cell's surface membrane," explains Ingber. Inside the cell, they're hooked to the cytoskeleton. Outside, they latch onto a framework known as the extracellular matrix - a fibrous scaffolding to which cells are anchored in our bodies.

Ingber and his colleagues have shown that when integrins move, the cytoskeleton stiffens. They did it by coating small magnetic beads, about 1 to 10 microns in size, with special molecules that bind to integrins. They attached the beads to the integrins and then applied a magnetic field.

"The beads turned and tried to align with the field, just like a compass needle would want to align with the earth's magnetic field," explains Ingber. The beads twisted the integrins and, in turn, tweaked the cytoskeleton. As more stress was applied, the cytoskeleton became stiffer and stiffer. In fact, it become so stiff that the beads couldn't be turned much past a few degrees!

more Cytoskeletons of human endothelial cells glow green in this immunofluorescent micrograph. The filaments meet in triangular structures resembling a geodesic dome - an example of tensegrity.

Tugging on integrins not only caused the cytoskeleton to stiffen, it also activated certain genes. "Activating a gene" means coaxing a gene to generate RNA and proteins. That's important because proteins are little messages that signal the cell to take action. Tickling the cytoskeleton, it seems, can make cells switch between different genetic programs.

Even before the magnetic bead experiment, Ingber's group at Harvard had already discovered a link between cell geometry and cell behaviour. In one experiment they forced living cells to take on different shapes - spherical or flattened, square or round - by placing them on tiny adhesive islands of extracellular matrix. Cells that were flat and stretched tended to divide. Cells that were round and cramped tended to die.

Says Ingber: "Mechanical restructuring of the cell and cytoskeleton apparently tells the cell what to do."

Very flat cells with taut cytoskeletons somehow sense that more cells are needed-to cover a cut, for example. Rounder, cramped cells might sense an overpopulation problem and decide it's time to die and make room for others. In either case, they are responding to a control system in which the shape-shifting cytoskeleton serves as a switching mechanism.

The potential implications of this research are vast - and not limited to space travel. It has already led to a prospective cancer treatment based on changes in cell shape. And it could provide new treatments for osteoporosis, cardiac disease, lung problems and developmental abnormalities. Every tissue in the body, says Ingber, has some disease that results from cells responding abnormally to mechanical forces.

"By pursuing the question of how cells sense gravity we've uncovered entirely new aspects of cell regulation."

Ingber believes that tensegrity is a core organising principle of the entire physical world. Self-stabilizing structures form spontaneously at every scale - cytoskeletons are merely one example. Another would be spherical carbon molecules called "BuckyBalls" that look like atomic soccer balls. Clay molecules also arrange themselves into tensegrity patterns that some researchers think harboured the first microscopic life forms on Earth. Even the universe itself, with its black holes (compression) and gravitationally linked galaxies (tension), may be a tensegrity structure.

"I gave a talk once at NASA on evolutionary biology," he recalls. "The last slide of my talk was a picture of the universe: super clusters of galaxies. Next to it was a one of capillary cells in a dish, formed into networks. The two pictures looked identical."