Correlated Parameter Fit of Arrhenius Model for Thermal Denaturation of Proteins and Cells

• DOI: 10.1007/s10439-014-1100-y
• Publication Date: 2014-09-09T13:25:34Z
• Authors: Zhenpeng Qin; Saravana Kumar Ba...; Willem F. Wolkers; John A. Pearce; John C. Bischof
• Keywords: Protein Denaturation; 0303 health sciences; 03 medical and health sciences; Hot Temperature; Cell Line, Tumor; Spectroscopy, Fourier Transform Infrared; Humans; Serum Albumin, Bovine; Collagen; Models, Biological; Peptide Fragments; Cell Line

Thermal denaturation of proteins is critical to cell injury, food science and other biomaterial processing. For example protein denaturation correlates strongly with cell death by heating, and is increasingly of interest in focal thermal therapies of cancer and other diseases at temperatures which often exceed 50 °C. The Arrhenius model is a simple yet widely used model for both protein denaturation and cell injury. To establish the utility of the Arrhenius model for protein denaturation at 50 °C and above its sensitivities to the kinetic parameters (activation energy E a and frequency factor A) were carefully examined. We propose a simplified correlated parameter fit to the Arrhenius model by treating E a, as an independent fitting parameter and allowing A to follow dependently. The utility of the correlated parameter fit is demonstrated on thermal denaturation of proteins and cells from the literature as a validation, and new experimental measurements in our lab using FTIR spectroscopy to demonstrate broad applicability of this method. Finally, we demonstrate that the end-temperature within which the denaturation is measured is important and changes the kinetics. Specifically, higher E a and A parameters were found at low end-temperature (50 °C) and reduce as end-temperatures increase to 70 °C. This trend is consistent with Arrhenius parameters for cell injury in the literature that are significantly higher for clonogenics (45-50 °C) vs. membrane dye assays (60-70 °C). Future opportunities to monitor cell injury by spectroscopic measurement of protein denaturation are discussed.