Procyanidin C1 Location, Interaction, and Aggregation in Two Complex Biomembranes

Procyanidins are known for their many benefits to human health and show a plethora of biological effects. One of the most important procyanidin is the procyanidin trimer C1 (PC1). Due to its relatively high lipid–water partition coefficient, the properties of PC1 could be attributed to its capability to interact with the biomembrane, to modulate its structure and dynamics, and to interact with lipids and proteins, however, its biological mechanism is not known. We have used all-atom molecular dynamics in order to determine the position of PC1 in complex membranes and the presence of its specific interactions with membrane lipids, having simulated a membrane mimicking the plasma membrane and another mimicking the mitochondrial membrane. PC1 has a tendency to be located at the membrane interphase, with part of the molecule exposed to the water solvent and part of it reaching the first carbons of the hydrocarbon chains. It has no preferred orientation, and it completely excludes the CHOL molecule. Remarkably, PC1 has a tendency to spontaneously aggregate, forming high-order oligomers. These data suggest that its bioactive properties could be attributed to its membranotropic effects, which therefore supports the development of these molecules as therapeutic molecules, which would open new opportunities for future medical advances.