Nano DSC: What To Consider When Choosing A Baseline And Model

One way to analyze the stability of a macromolecule in dilute solution is to determine the changes in the partial molar heat capacity of the macromolecule at constant pressure (ΔCp). The change in the heat capacity of a compound reflects its ability to absorb heat and experience a defined increase in temperature. During the unfolding process, not only is the macromolecule denaturing but also the water molecules begin to restructure as more non-polar sidechains are exposed. This is what leads to a shift in the baseline, as there is a change in the heat capacity when going from the native to unfolded structure. The other parameters from a typical DSC curve are TM, which is the temperature at which half the macromolecules are folded, and the other half unfolded. The integration of the transition reflects ΔHcal, the enthalpy measured directly from the Nano DSC during the unfolding event. Finally, the full width half max (FWHM) value can be determined, which can be used to compare cooperativity between different samples.

There is a lot of information that can be obtained directly from the analysis curve without needing to model the data, however, choosing to model DSC data can give additional insight into the unfolding process of a macromolecule or be helpful to deconvolute a multiple transition thermogram. Explore general guidelines for choosing the correct baseline and DSC model. It is important to note there are times where one could choose from multiple models and still be correct. For this reason, it is key to be consistent on the model type that is chosen when more than one could apply. This allows for better direct comparison of data between samples.