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Updated 10:00 AM January 15, 2007




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Scientists discover rules for virus shapes

A surprising discovery out of the University about how nanoparticles self-assemble into structures that resemble viruses gives scientists key insight into how common, disease-producing viruses might form in our bodies.

This new understanding brings researchers closer to making synthetic viruslike particles in the lab that could be used to help stop viruses from replicating, or could be used as stealth viruses to deliver drugs.

The team also was able to achieve a shape identical to those of polyhedral-shaped clusters that form when a few plastic microspheres, called colloids, stick together in a shrinking fluid droplet—shapes previously identified in a study from the University of California, Santa Barbara. The U-C results, reported in the journal Science several years ago, were considered a monumental breakthrough because of their precision and the similarity of some of them, shapewise, to simple molecules, says Sharon Glotzer, chemical engineering professor and corresponding author on the U-M paper.

"An exciting aspect of our findings is this new connection between the shapes of certain viruses and those of colloidal 'molecules,' " says Glotzer, who also has appointments in materials science and engineering, physics, macromolecular science and engineering, and applied physics. "Our simulations prove that the shapes are all part of the same sequence that results from simple thermodynamic and mathematical ingredients. This is fundamentally new and unexpected."

The findings, published in the Proceedings of the National Academy of Science, give a simple set of rules for scientists to follow when trying to coax particles to self-assemble into virus-shaped shells. Viruses are nanometer-sized particles made of proteins containing DNA or RNA that allow them replicate and infect cells in the body, and many are shaped like a 20-sided polyhedron known as an icosahedron. Until now, scientists have not understood why many viruses in our bodies form that shape, but the team's results present the minimal conditions necessary to produce them.

Using computer simulations, chemical engineering doctoral student Ting Chen, Research Associate Zhenli Zhang and Glotzer self-assembled tiny particles into precise, convex shapes. To their surprise, they discovered an entire sequence that includes the shapes of several common viruses, as well as the colloidal shapes.

The team predicts there are two main rules to make these shapes in the lab: The particles used must attract each other (or be attracted to the same central point), and the particles must always be on a convex surface. When the shape contains just a few particles, convexity arises naturally. When it is comprised of many more particles, as needed for viruses, the convexity must be imposed.

"If you force tiny spheres to assemble on the outer surface of a balloon, for example, the balloon provides a convex surface," Zhang says. "Imagine now shrinking the balloon; at some point the spheres will all touch and rearrange into a tightly packed structure. These are the structures our simulations predict."

In a yet unpublished companion paper, Chen (now a postdoctoral researcher at Princeton University) and Glotzer show that other convex "balloons" can produce other known virus shapes, including elongated shapes.

"Beyond disrupting virus replication and other nanomedicine applications," Glotzer says, "there are many potential applications for constructing tiny, precise shells of predictable shape from nanoparticles. With the design rules now in hand, the possibilities are enormous."

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