Flow enhanced protein crystallization at the air/water interface

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CBET-0755968HirsaThe ability to describe and use protein structure has enabled the rational design of new drugs and pharmacological agents. Many advances in understanding of biological systems at the molecular level have been made possible through detailed structural studies of proteins and nucleic acids. However, proteins must first be crystallized to use techniques that yield a precise description of their structure. In contrast to growing protein crystals in the bulk, 2D protein crystallization greatly simplifies both the theoretical and experimental aspects of protein studies. For example, 2D systems are not affected by gravity, an issue that plagues crystallographers with no affordable remedy. Two-dimensional protein crystallization at the air/water interface entails the specific binding of a protein to a lipid monolayer containing a ligand. The protein streptavidin, in solution, has been successfully crystallized at the air/water interface where a lipid monolayer containing a ligand, biotin, has been spread. The strong affinity between streptavidin and biotin initiates crystal formation at the interface under suitable conditions. The PIs will investigate the effects of flow in a system consisting of a stationary open cylinder driven by the constant rotation of the floor, in the axisymmetric flow regime over a wide range of Reynolds numbers. The PIs have recently discovered interface s sheared by flow can induce crystallization under conditions where none would otherwise occur. The PIs have discovered that flow can also produce a new form of crystal where the protein molecules appear to pack in a linear array, analogous to nano-wires, but much longer and perfectly straight. The PIs plan to investigate the macroscale flow phenomena associated with these new crystals. The PIs expect that varying the Reynolds number will regulate the nucleation rate and growth separately, which is a challenge for crystallographers. There are a vast number of proteins that have not been successfully crystallized by conventional means, and if flow-induced crystallization can improve the yield, then the effort here would be a resounding success. The multidisciplinary senior team (from mechanical engineering and applied mathematics), with its strong record of productive collaboration, will provide an excellent opportunity to educate graduate and undergraduate students in an exciting emerging field coupling hydrodynamics and protein studies.