Submitted to: Journal of Agricultural and Food Chemistry
Publication Type: Peer reviewed journal
Publication Acceptance Date: 7/2/2008
Publication Date: 8/2/2008
Citation: Sirk, T.W., Brown, E.F., Sum, A.K., Friedman, M. 2008. Molecular Dynamics Study on the Biophysical Interactions of Seven Green Tea Catechins with Cell Membranes. Journal of Agricultural and Food Chemistry. 56:7750-7758. Interpretive Summary: Catechins (flavonoids), which are present in many widely-consumed foods including apples, berries, chocolate, grapes, and teas, are reported to be associated with a large number of beneficial health effects. Previously we reported that relative antimicrobial activities of tea catechins paralleled activities against human cancer cells. One mechanism by which catechins operate at the cellular-molecular level involves interaction with components of cell membranes leading to prevention of binding of bioactive molecules such as enzymes to receptor sites and/or disruption of cell membranes resulting in leakage of cell components followed by cell death. Large differences in biological activities of structurally different catechins may to be due to differences in relative affinities to lipid and glycoprotein layers of cell membranes. To provide additional insights about the possible interactions of catechins with components of cell membranes, we explored (in a collaborative study carried out at the Departments of Chemical and Mechanical Engineering, Virginia Polytechnic Institute and State University, Blacksburg) biophysical interactions of seven tea catechins with lipid bilayers (model cell membranes) by means of molecular dynamics simulations. The results of the present study show that hydrogen bonding of phenolic hydroxyl groups of catechins to cell membranes may be correlated with antimicrobial and other beneficial effects of catechins. The described findings are not only of fundamental interest, but also have practical implications for our understanding of how catechins inhibit pathogenic bacteria, bacterial toxins, and cancer cells.
Technical Abstract: Molecular dynamics simulations were performed to study the interactions of bioactive catechins (flavonoids) commonly found in green tea with lipid bilayers, as model for cell membranes. Previously, a number of experimental studies rationalized catechin’s anticarcinogenic, antibacterial, and other beneficial effects in terms of physicochemical molecular interactions with the cell membranes. To contribute toward understanding the molecular role of catechins on the structure of cell membranes, we present simulation results for seven catechins in lipid bilayer systems representative of HepG2 cancer cells. Our simulations show that the seven tea catechins evaluated have a strong affinity for the lipid bilayer via hydrogen bonding to the bilayer surface, with some of the smaller catechins able to penetrate underneath the surface. Epigallocatechin-gallate (EGCG) showed the strongest interaction with the lipid bilayer based on the number of hydrogen bonds formed with lipid headgroups. The simulations also provide insight into the functional characteristics of the catechins that distinguish them as effective compounds to potentially alter the lipid bilayer properties. The results on the hydrogen-bonding effects, described here for the first time, may contribute to the proposed multiple mechanisms of action of catechins in microbes, cells and tissues.