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Scientists discover rules for some common virus shapes

University Of Michigan : 16 April, 2007  (Technical Article)
A surprising discovery at the University of Michigan 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.
A surprising discovery at the University of Michigan 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 virus-like 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 U-M team also achieved 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. Those results, out of University of California, Santa Barbara, were reported in the journal Science several years ago and were considered a monumental breakthrough because of their precision and the similarity of some of them, shape-wise, to simple molecules, said Sharon Glotzer, chemical engineering professor at U-M and corresponding author on the paper.

'An exciting aspect of our findings is this new connection between the shapes of certain viruses and those of colloidal 'molecules',' Glotzer said. '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 U-M team's findings, published in the Proceedings of the National Academy of Science this week, 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 that contain DNA or RNA that lets 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 U-M team's results present the minimal conditions necessary to produce them.

Using computer simulations, U-M chemical engineering PhD 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 of shapes that includes several common viruses as well as the colloidal shapes.

The team predicts that 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, the convexity arises naturally. When the shape contains 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 said. '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 companion paper not yet published, 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,' said Glotzer, '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.'

Glotzer also has appointments in materials science and engineering, physics, macromolecular science and engineering, and applied physics.
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