Anticarcinogenic trimethoxybenzoate of catechin stabilizes the liquid crystalline bilayer phase in phosphatidylethanolamine membranes

Abstract

The anticarcinogenic properties of catechins stand out among the great variety of biological actions attributed to these compounds. The capacity of catechins to interact with lipids and their participation in membrane related processes points out to the membrane as their potential site of action. Phosphatidylethanolamine is an abundant phospholipid in mammalian membranes that has tendency to form non lamellar phases, it is associated with important cellular processes, and it has been related to cancer. In order to shed light into the molecular effect of the anticarcinogenic 3,4,5-trimethoxybenzoate of catechin (TMBC) on lipid polymorphism and membrane structure and dynamics, we present a combined experimental and computational study of the interaction between this semisynthetic catechin and biomimetic membranes composed of unsaturated phosphatidylethanolamine. Our experimental evidence reveals that TMBC is readily incorporated into unsaturated phosphatidylethanolamine system where it is able to shift the gel to liquid crystalline phase transition temperature to lower values, decreasing the cooperativity and the enthalpy change of the transition. The presence of TMBC is able to promote the formation of gel phase immiscibility and to block the formation of the inverted hexagonal phase. In the bilayer liquid crystalline phase, the catechin decreases the interlamellar repeat distance, it increases the fluidity of the membrane, and it alters the hydrogen bond pattern of the interfacial region of the bilayer. Our molecular dynamics results concur with the experimental data and locate TMBC forming different domains near the interfacial region of the bilayer where it modifies the lateral pressure profile of the membrane leading to a stabilization of the bilayer in the liquid crystalline phase and to a potential alteration of the function of the membrane.