Pixar software could help simulate molecular interactions inside cells.
Computer programs like those used in animated movies such as Shrek could soon be helping more cell biologists explain hypotheses — or even to make new discoveries, according to scientists presenting work in San Diego this month at the meeting for the American Society of Cell Biology.
"We want to be able to make predictions," says Adrian Elcock of the University of Iowa in Iowa City. "At the very least we want our models to reproduce known behaviours." Elcock is simulating the movement of proteins and other big molecules inside virtual bacterial cells. He built models from known data — including the atomic structures of proteins and concentrations of the 50 most abundant macromolecules in Escherichia coli — and then factored in how the molecular structure of each might cause proteins to stick to each other. His model nicely reproduces established data showing that green fluorescent protein diffuses approximately 10 times more slowly in the crowded environment of a bacterial cell than in a test tube.
"Animation is seen as more eye candy than anything," says Janet Iwasa of Harvard Medical School in Boston. "That could change." Iwasa, who chaired the session on three-dimensional visualization, creates animations for researchers to help them explain their hypotheses to each other. She says the impetus for the session began when one of her animations — showing the protein clathrin, which helps cells take in material from the cell membrane — won the CellDance competition at last year's meeting (see movie). Demand for her services often comes after scientists see an animation representing a competing hypothesis and want to be able to show their own view of what's happening, she says.
Our brains don't cope well with following the myriad interactions inside cells, says Jonathan Alberts of the University of Washington in Friday Harbor. "Our intuition is fragile in this regard. We need a tool to help us understand." Alberts simulated cellular parts such as motor proteins and actin filaments, programmed them to obey a few mathematical rules reflecting physical forces, and saw that they were able to reproduce their behaviour in cells on his computer screen. Biological systems are robust, he reasoned, so "all we really need to do, we hope, is get things about right, and we will see some emergent properties".
Alberts showed his work modelling the contractile ring in fission yeast, a belt of proteins that assembles around a rod-shaped cell and constricts to divide the cell in two. He fed parameters into the model and watched. At first all seemed well; the proteins formed nodes and gathered into a ring. Then they collapsed in a clump. Still, he says, the preliminary results are encouraging. "You really see self-organization happen."
Many scientists already use an array of software to visualize proteins in three dimensions, but these programs do not show how proteins behave in their cellular context. For that, scientific animators turn to Maya — the same program Pixar and other Hollywood firms rely on. But getting the scientific data into the platform is a major roadblock, says Gaël McGill, chief executive of Digizyme, who teaches molecular visualization at Harvard Medical School in Boston. "It's the most common question we have: Can we embellish Maya so that it's easier for scientists to bring the data in?"
McGill announced free software called Molecular Maya Toolkit that allows researchers to automatically bring protein structures into a cellular landscape using data from online repositories. Meeting attendee Patrick Huehls of Indiana University in Bloomington believes the toolkit will be highly used, and not only by those hoping to bring science to nonexperts. Scientists themselves are coming to depend on animation, he says. "It's becoming more part of discovery than an endpoint."