Quantifying the effect of DMSO on protein folding

Dimethyl sulfoxide (DMSO) is a small, amphipathic molecule widely used as an aprotic solvent in scientific research and as an intracellular cryoprotective agent (CPA) to protect mammalian or bacterial cells from damage during cooling and rewarming processes. However, the scientific rationale behind the concentration-dependence of DMSO CPA function is very limited, and there are currently no guidelines outlining which concentration should be used. The non-standard use of DMSO as a CPA has inhibited differentiation of human stem cells and resulted in cardiovascular failure from cells preserved for the use of transplant therapy. Having a clear understanding of how DMSO affects biomolecular structure and stability, and particularly how it affects these properties in the native cellular environment, is necessary to inform the proper use of DMSO in cryopreservation. I propose to study the effects of DMSO concentration on protein folding in vitro and in cells, as proteins are the most abundant macromolecule in cells and promote cellular toxicity when misfolded. This study will provide a model to assess the role of DMSO on protein folding in cells to determine clearer guidelines in the use of DMSO as a CPA.Bachelor of Art