3-D AFM Could Advance Understanding of Proteins

An advanced 3-D atomic force microscope will allow the study of membrane proteins in conditions similar to those found in the body, an improvement that could lead to increased understanding of proteins on the microscopic level and faster drug therapies.

The study of complex proteins that allow information and molecules to pass into and out of a cell has long been restricted by the limitations of one-dimensional force microscopes. Preparation requirements mean that a specimen could not be studied as it would behave in its normal environment.

A 3-D atomic force microscope developed by researchers at the University of Missouri. Images courtesy University of Missouri’s Department of Physics and Astronomy and Department of Biochemistry.

Researchers at the University of Missouri (MU), using a traditional one-dimensional force microscope as a guide, have added another laser to measure the second and third dimensions of tip movement. This provided real-time access to the measurement of peaks and valleys in the membrane protein and dynamic changes in those structures.

Researchers scattered a focused laser directly off an atomic force microscope tip apex to rapidly and precisely measure the tapping tip trajectory in a 3-D space.

“Using this new laser, we collect the back-scattered light from not only the cantilever holding the needle, but also the tip of the needle that gives additional measurements,” King said. “This added flexibility allows us to collect information faster and allows our microscope to work in near-native conditions in fluid like those found in the cell, yielding more realistic results.”

By studying how the shape of proteins change, researchers can determine how drugs bind and interact with cells, said Gavin King, assistant professor of physics and astronomy in the College of Arts & Science at MU, and joint assistant professor of biochemistry. The membrane protein information can assist pharmaceutical companies in determining which molecules to pursue.

The work was published in Nano Letters.

For more information, visit www.missouri.edu.