Sculpting life
It's a standby of high school biology courses the world over: The basic blackboard drawing of a cell that looks like a squishy puddle, a soggy balloon, a giant egg, with little organs floating about inside.
It's a wonder that the squishy cells stacked up could give rise to the quite solid human body. Well, they don't.
Children's Hospital's Donald Ingber has made breakthroughs over the years that have convinced scientists that cells have a flexible yet strong internal architecture, a rigid weave of biological girders. And Ingber has shown that manipulating the shape of the cell can drastically alter its behavior, even causing it to commit suicide.
It was an insight that Ingber first pondered in a sculpture class as a Yale undergraduate. He had settled on medicine, but his interests ranged wide: art, theater, literature.
"The earlier you get into crossing boundaries, the easier it is, the more facile you get," Ingber says.
For a sculpture class assignment, he used just a few sticks and wires to build sturdy yet flexible sculptures. He began to see how the art form might reveal something fundamental about biology's own building block, the cell.
Later he conducted studies showing cells had sculpturelike support structures, a quality he labeled "tensegrity," a term first coined by futurist architect R. Buckminster Fuller. In Ingber's model, tiny microtubules in cells served as compression-bearing struts, microfilaments were tension bearers, and other filaments connected this skeleton to the cell nucleus. It was a durable but not rigid infrastructure.
Ingber's lab later showed that stretching a cell until it becomes flat causes it to divide; if you make it round, it commits suicide; if you leave it be, it functions normally. The state of a cell's skeleton, Ingber says, affected the genes it expresses.
For many biologists, Ingber's work was central in establishing that biological processes were really just physical processes that could be engineered like bridges and buildings. These days, he's just as likely to be chatting up engineers, physicists, and computer programmers as doctors or biologists.
His work may one day help treat the many diseases involving cell distortion. And it could offer insights into life itself: How did life emerge from inanimate matter? How did it take shape?
Though Ingber has published hundreds of scholarly articles and runs a prestigious laboratory, he still remembers vividly when his ideas merging art and science seemed to jell. It was a cold Christmas break at Yale. Ingber spent it ensconced in the library. And as he pored through books, it all began to come together.
"It was like touching the heartstrings of the universe," he says. 