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Measuring a Microverse With a Universal Yardstick

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Measuring a Microverse With a Universal Yardstick

September 25, 1997

January 5, 1998 update: Hi-resolution JPGs added for print media.

A device that helped show how the universe is put together is being pressed into service to help us understand how molecules assemble themselves into crystals. Lessons from the Interferometer Protein Crystal Growth (IPCG) apparatus, scheduled to go to the Mir space station this week, will help scientists determine the best ways to grow protein crystals to fight disease.

While scientists have been growing protein crystals in space since the mid-1980s, and great progress has been made in understanding the makeup of many crystals, their knowledge of how crystal growth works has serious gaps.

"Ultimately, what everybody wants to know is how and why," explained William Witherow, an IPCG co-investigator at Marshall Space Flight Center; Dr. Marc Pusey of Marshall also is a co-investigator. The principal investigator is Dr. Alex McPherson of the University of California at Riverside. "A lot of the research effort to date is going into the shotgun approach."

IPCG test cell
A tiny, fragile test cell, like this one, will hold about 4 ml of protein solution. This view looks through the face of the test cell to the mirror that serves as part of the Michelson interferometer.

Analyzing crystals of proteins is the best way to understand their structure. From this, scientists can determine how bacteria, viruses, and our own bodies work, and how best to design drugs to cure disease. Space often proves to be the best place to grow protein crystals without the defects that often affect crystals grown on Earth.

Scientists usually devise experiments involving different initial mixtures designed to promote crystal growth. With experience, they learned which blends work best - but not always why they work best.

"All they got back are the protein crystals themselves," Witherow said, "but the investigators still don't know how the crystals grew or why."

The IPCG experiment will look at that how and why.

Crystals grow as molecules move through a fluid, bump into one another, and latch into position to build a repeating pattern, like a child's building blocks. The process involves diffusion as molecules migrate from an area of high concentration to an area of low concentration (the depleted area just next to the crystal).

Many factors influence the growth rate, including contaminants (which may move faster - or slower - than the proteins you want to grow), how much salt is in the solution (salt collects water and raises the protein concentration to force crystallization), the acid-base balance (pH), temperature, and so on.

These also affect the liquid's density and thus its index of refraction, how it will bend light. This is where Michelson is brought back into service.

In the mid-1880s, Michelson and Edward Morley were trying to prove that light was carried through the universe by a mysterious substance called "the luminiferous ether" (nothing to do with laughing gas). They reasoned that if this was true, then light would be slowed as it traveled "upwind," while light traveling "crosswind" would not be affected. (The "wind-speed" would be due to the Earth's motion around the Sun and through space). Michelson developed an interferometer, a device which splits a beam of light, sends it in two different directions, then recombines the two beams.

interferometery pix 1interferometery pix 2If the light has been changed in any way, the beam will paint a series of light circles where peaks combine with peaks to make the light more intense, and dark circles where peaks combine with valleys to zero the light out, like the banded patterns shown at left in an IPCG ground test.

Michelson and Morley wound up proving that the luminiferous ether does not exist (and Michelson won the Nobel Prize in physics in 1907).

Meanwhile, they had invented an exceptionally powerful tool that could also be used to measure effects on scales much smaller than the cosmos.

In the IPCG, it is combined with tools that Michelson could not have envisioned. The heart of the device is a Michelson interferometer comprising a beam-splitter prism to split, then recombine the light beams, a laser as the light source, and a microscope to enlarge the view.

The target is a wafer-thin crystal growth chamber about the size and shape of a throat lozenge. It will be filled with a solution of lysozyme, a common protein found in eggs.

"They use it as a benchmark because it's so well known and characterized," Witherow said.

The backside of the cell is silvered to serve as one mirror in the interferometer. The other leg is a reference mirror. Light is split, directed onto the two mirrors and back again, recombined, enlarged by a 20-power microscope, and projected onto a video camera. The interference fringes will be enhanced by a liquid crystal phase modulator and a polarizing filter.

IPCG optical systemThe IPCG optical system is shown uncovered before integration for flight. For a full image and for details, read the IPCG Fact Sheet.

A laptop computer will record about 4,050 images for study on Earth after the mission.

Part of the challenge of designing the system was fitting it all into a box about the size of an overhead bin on an airplane (the approximate size of the Shuttle middeck locker) for use inside the glovebox in Mir's Priroda science module. Six fluid systems will be carried, each with different blends of lysozyme and other chemicals.

The system is scheduled to return to Earth on STS-89 in early 1998.


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Author: Dave Dooling
Curator: Bryan Walls
NASA Official: John M. Horack