Investigation of the Properties of Liquids in the Porous Networks of Macromolecular Crystals

Whitman College, Walla Walla WA

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Abstract

Abstract Knowledge of macromolecular structure is important for understanding and developing treatments for a diverse array of diseases. Many macromolecular structures are determined via diffraction techniques, for which a key step is to grow crystals of the macromolecule of interest. The crystals are highly packed nanoporous materials in which an ordered array of biological macromolecules is permeated with a network of nanometer-sized pores. The long-term goal of this project is to understand the interplay between the macromolecules and the liquid inside the pores and how this affects the response of the crystals and their substituent macromolecules to changes in external environment such as temperature and solution conditions. This is important for two main reasons. First, macromolecular crystals often undergo changes in their environmental conditions as part of their analysis. Second, the interplay between the macromolecules and solvent is key in understanding functional aspects of the macromolecules, not only in crystals but also in the similarly highly packed environment of the cell. Here we focus on how the environment of the porous network affects the properties of the liquid inside. By using single particle fluorescence tracking, we will measure diffusion of probes within the porous network of macromolecular crystals. Comparing these results to diffraction experiments will elucidate the diffusion and flow characteristics of the liquid in the pores. Hence information that can lead to more gentle treatment of these delicate samples will improve the overall quality of structure determined via crystallography and better understanding of the behavior of liquids in highly packed environments. The long-term effects of improved understanding of the response of macromolecular crystals to changes in environment will be to ensure that the highest quality diffraction possible is recorded from each crystal. This will (a) improve the average quality of structures determined by X-ray crystallography and (b) make the more difficult crystallographic problems more tractable. This work will impact public health by improving the reliability of biological interpretations based on macromolecular structures, and will increase the likelihood that the structure of any particular molecule with a potential impact on health can be efficiently determined. In the long term, this would improve our understanding of the causes of, and facilitate treatments for, diseases resulting from the alteration of macromolecular structure and function by either genetic or environmental factors.