Molecular-level interaction of dopamine with lipids studied by sum frequency generation spectroscopy

Dopamine is a clinically essential pharmaceutical agent extensively used in cardiology and emergency medicine. During the drug treatment, interactions between dopamine and lipid membranes are unavoidable. However, their molecular-level interaction remains insufficiently understood. In this research, sum frequency generation spectroscopy was utilized to investigate the molecular-level interaction of dopamine with the negatively charged phosphatidylglycerol (PG) lipid bilayer, in real time and in situ. Our results reveal that both the outer and inner PG leaflets remain unaffected at a low dopamine concentration of 1.0 mM. In contrast, at 10 mM dopamine, sight perturbations to the outer PG leaflet were observed due to the hydrogen bonds and electrostatic interactions formed between them. The average tilt angles of the CD₃ groups were calculated to be 33° and 38° before and after the addition of 10 mM dopamine, respectively. To the best of our understanding, this work experimentally quantified the dopamine-induced orientation variations of lipid molecules in a bilayer for the first time. These findings provide molecular-level insights into dopamine-membrane interactions, offering potential guidance for the development of new cardiovascular therapeutics involving dopamine-related membrane processes, such as treatments for hypotension, shock, and heart failure.