Effect of $Me2SO$ on Membrane Phase Behavior and Protein Denaturation of Human Pulmonary Endothelial Cells Studied by In Situ FTIR Spectroscopy

Fourier transform infrared spectroscopy (FTIR) provides a unique technique to study membranes and proteins within their native cellular environment. FTIR was used here to study the effects of dimethyl sulfoxide $(Me2SO)$ on membranes and proteins in human pulmonary endothelial cells (HPMECs). Temperature-dependent changes in characteristic lipid and protein vibrational bands were identified to reveal the effects of $Me2SO$ on membrane phase behavior and protein stability. At $Me2SO$ concentrations equal to or below 10% (v/v), $Me2SO$ was found to decrease membrane conformational disorder. At higher $Me2SO$ concentrations (15% v/v), however, membrane conformational disorder was found to be similar to that of cells in the absence of $Me2SO$⁠. This effect was observed over a wide temperature range from $90°C$ down to $−40°C$⁠. $Me2SO$ had no clear effects on cellular proteins during freezing. During heating, however, $Me2SO$ had a destabilizing effect on cellular proteins. In the absence of $Me2SO$⁠, protein denaturation started at an onset temperature of $46°C$⁠, whereas at 15% $Me2SO$ the onset temperature of protein denaturation decreased to $32°C$⁠. This implies that in the presence of $Me2SO$ the onset temperature of protein denaturation is lower than the normal growth temperature of the cells, which could explain the well documented toxic effect of $Me2SO$ at physiological temperatures. $Me2SO$ destabilizes cellular proteins during heating and decreases membrane conformational disorder over a wide temperature range.