Highlights

Tiny Device Helps View Protein Structure

Researchers in the Common Fund's Structural Biology Research program have engineered a tiny new device to optimize the conditions needed for proteins to form crystals so their function can be studied in cells. Knowing a protein's structure can provide clues about how it functions normally, how it behaves abnormally in a diseased cell, and how its function may be restored by drugs that target specific parts of the protein that control activity

X-ray crystallography is a powerful tool to make high resolution images of protein structure by identifying the position of individual atoms in three-dimensional (3-D) space and then converting them into a topological map of the protein. However, for X-ray crystallography to work, the protein molecules must be concentrated and stacked in an orderly fashion into a protein crystal. Otherwise, the protein molecules just flop around, making it impossible to accurately pinpoint the position of the individual atoms. This is challenging because proteins are very finicky about the conditions under which they will form well-ordered crystals and very large amounts of proteins are usually needed to form crystals for analysis of 3-D structure.

Dr. Rustem Ismagilov at the University of Chicago has developed a microfluidic device called a "SlipChip" that allows researchers to explore the ideal conditions that can support the crystallization of a protein using very small amounts. The SlipChip can simultaneously test 160 different conditions that may support protein crystal formation. The protein of interest is injected in to a central port on the SlipChip where it flows through microfluidic channels and enters 160 nanometer-scale sized wells grouped into 16 separate units containing 10 wells each (see figure). The protein in each unit is subsequently exposed to a different precipitant, that is, a chemical solution that may support crystallization. This occurs after each precipitant is injected into one of the 16 units where it flows into 10 wells that sit underneath the protein-containing wells and the two are brought in to contact by "slipping"; the protein wells closer to the precipitant wells. The physical distance between the protein and precipitant wells on the SlipChip gradually increases from the first well to the tenth well, varying the time the protein and precipitant interact with each other. Precise control of this timing is important for some proteins that will not form well-ordered crystals if the interaction time is too fast. The beauty of the SlipChip is that it increases the chances of finding the optimum conditions for proteins and precipitants to interact so protein crystals form.

Reference:
Li L, Du W, and Ismagilov RF. Multiparameter screening on SlipChip used for nanoliter protein crystallization combining free interface diffusion and microbatch methods. J Am Chem Soc. 2010 Jan 13;132(1):112-9. PMID: 20000709.

Up to Top