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2014

Watch Proteins Do the Jitterbug
New York Times, April 10, 2014
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If you could shrink down to the size of a molecule and fly into a cell, what would you see?

In 2006, a team of scientists and illustrators offered a gorgeous answer in the form of a three-minute video called “The Inner Life of the Cell.” Nothing quite like it had ever been made before, and it proved to be a huge hit, broadcast by museums, universities and television programs around the world.

The video was a collaboration between BioVisions, a scientific visualization program at Harvard’s department of molecular and cellular biology, and Xvivo, a scientific animation company in Connecticut.

Delving into the scientific literature, the scientists and animators created a video about an immune cell. The cell rolls along the interior wall of a blood vessel until it detects signs of inflammation from a nearby infection.



We dive into the cell to see what happens next. Molecules swim through the cell like dolphins, relaying the signal from the outside. Certain genes switch on, and the cell makes new proteins that are put into a blob called a vesicle. An oxlike protein called kinesin hauls the vesicle across the cell, walking along a molecular cable.

Once the vesicle reaches its destination, it releases its cargo. The new proteins cause the immune cell to stop rolling, and it flattens out and slips between the cells that make up the blood vessel wall so that it can seek out the infection.

“The Inner Life of the Cell” was made possible by advances on many scientific fronts.

In recent years, scientists have learned a great deal about the shapes of biological molecules, for example. They can use powerful computers to visualize the molecules in action.

The video was so entrancing that it was easy to forget that it was not raw footage captured by some microscopic GoPro camera. It was a piece of art. The scientists and animators made choices about what to show, and how to show it.

For one thing, they left out just about all the proteins, giving the cell the look of a nearly empty ocean. “The interior of a cell is incredibly crowded,” said Michael Astrachan, the president and creative director of Xvivo.

Alain Viel, the director of undergraduate research at Harvard and a member of the BioVisions team, likened the inside of a cell to a rush-hour subway platform. “If there’s a big crowd in front of you, there’s a good chance you might not even see the train,” he said.

Dr. Viel and his colleagues also chose to show the proteins moving with a stately grace. Real proteins, by contrast, are perpetually quivering. They pick up bits of energy from water molecules that bump into them, and they crash into other proteins and bounce off cell membranes.

Two years ago, BioVisions and Xvivo set out to upgrade their animations by capturing some of that messy complexity. They wanted to cram a virtual cell with proteins at a more realistic density, and then have them jitter and collide.

It turned out to be an enormous amount of work. The motion and appearance of each molecule had to be individually calculated, leading to a vast amount of data that put a strain on Xvivo’s computers.

Along with the scientific effort, the new video required aesthetic work. To allow viewers to distinguish among many kinds of molecules, the Xvivo animators had to search for the right scheme of colors and shadings.

Recently they unveiled the result of their efforts in a video called “Protein Packing”:



In this movie, we enter a neuron by diving through a channel on its surface. Once inside, we’re instantly surrounded by a swarm of molecules. We push through the crowd until we reach a proteasome, a barrel-shaped molecule that shreds damaged proteins so their components can be used to make new proteins.

Once more we see a vesicle being hauled by kinesin. But in this version, the kinesin doesn’t look like a molecule out for a stroll. Its movements are barely constrained randomness.

Every now and then, a tiny molecule loaded with fuel binds to one of the kinesin “feet.” It delivers a jolt of energy, causing that foot to leap off the molecular cable and flail wildly, pulling hard on the foot that’s still anchored. Eventually, the gyrating foot stumbles into contact again with the cable, locking on once more — and advancing the vesicle a tiny step forward.

This updated movie offers a better way to picture our most intricate inner workings. For one thing, it helps us to understand why we become sick. A number of diseases, such as Alzheimer’s and Parkinson’s, are caused when defective proteins clamp onto other proteins, creating toxic clumps.

In the 2006 version of the animation, it’s hard to imagine how two proteins in such a careful dance would bump into each other. In the new version, where proteins jostle past one another like commuters in a busy train station, it’s common sense.

The new movie helps us understand biology at a deeper level, too. In the 2006 version, we can’t help seeing intention in the smooth movements of the molecules; it’s as if they’re trying to get from one place to another. In reality, however, the parts of our cells don’t operate with the precise movements of the springs and gears of a clock. They flail blindly in the crowd. Our cells work almost in spite of themselves.

“I want people to say, ‘I can’t believe this is happening at all,'” said Mr. Astrachan.

Copyright 2014 The New York Times Company. Reproduced with permission.
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