We have recently demonstrated that low melting point organic salts, called ionic liquids, can be rationally designed to stabilize proteins against thermal denaturation by modulating solvent properties. By judicious choice of cation, anion, and functional groups, not only can the stabilization characteristics be tuned, but a range of physical properties, such as the pH, viscosity, and the extent of dissociation of the salt (i.e osmolality) can also be tailored to the application. We have also been able to modulate the cytotoxicity of ionic liquids by rational selection of anions. We propose to extend these exciting results to cellular applications, where many of the same features are desired in a cell stabilizing formulation. The determination and application of 'task-specific'molecular design rules will move preservation science beyond the standard trial and error approach with existing materials towards rationally designed cell protectants for specific tissue and storage requirements. Specifically we seek to:
Aim #1 : Determine the structural features and physical properties of ionic liquids that result in stabilizing associations and penetration of mammalian cell membranes.
Aim #2 : Determine the thermal-physical behavior and glass-forming characteristics of biocompatible ionic liquids in composition with water and sugar-based stabilizing molecules, such as trehalose.
Aim #3 : Establish the post preservation viability and shelf-life of cells stored in ionic liquid based preservation solutions using three different preservation methods: slow-cooling, rapid-cooling, and dehydration.
Cell-based therapeutics (e.g. stem cells used to treat certain cancers) must be stored at cryogenic temperatures, which results in very high storage and transportation costs. This research seeks to reduce these costs by investigating new materials that can enable cell-based therapies to be stored at higher temperatures.
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