S2: Effect of hydrophobic pollutants on biological membranes

Effect of hydrophobic pollutants on biological membranes: a simulation perspective


Luca Monticelli


French National Institute of Health


Senior Researcher


[1] K Simons, R Ehehalt, J Clin Invest (2002) 110, 597–603 [2] G Rossi, J Barnoud, L Monticelli, J Phys Chem Letters (2014) 5, 241-246 [3] J Barnoud, G Rossi, SJ Marrink, L Monticelli, PLoS Comp Biol. (2014) 10, e1003873



The first contact of exogenous materials with living organisms generally involves the interaction with a biological membrane. Understanding the interaction of exogenous materials with biological membranes is therefore a key step towards characterizing their biological activity, as well as the potential toxicity. Cell membranes have a complex chemical composition and lateral organization, and are generally fluid under physiological conditions – which makes it extremely difficult to study their structure and dynamics experimentally. Molecular simulations on model membranes can aid in the interpretation of experimental data on membranes, including their structure, dynamics, and interactions. In this presentation I will describe the effect of six different hydrophobic pollutants on the properties of model membranes, and in particular on their lateral organization. Cell membranes have a complex lateral organization featuring domains with distinct composition, also known as rafts, playing an essential role in cellular processes. Perturbation of membrane domains has major effects on the activity of raft-associated proteins and on signaling pathways [1], but it is not clear which chemical and physical properties determine domain perturbation. Using molecular simulations on model membranes, we identified two groups of molecules with distinct behavior: aliphatic compounds promote lipid mixing by distributing at the interface between liquid-ordered and liquid-disordered domains; aromatic compounds, instead, stabilize phase separation by partitioning into liquiddisordered domains and excluding cholesterol from disordered domains [2,3]. We predict that relatively small concentrations of hydrophobic species can have a broad impact on domain stability in model systems, which suggests possible mechanisms of action for hydrophobic pollutants in vivo.