Effects of Diacylglycerols (DAGS) and Arachidonic Acid (AA) on the Physical Properties of Model Lipid Bilayers: A Molecular Dynamics Simulations Study

DAGs are lipid molecules capable of triggering a wide range of biological responses. They serve as second messengers by regulating both the translocation to the membrane compartment and the activation of C1 domain-bearing proteins, but they are also involved in the activation of certain TRPC channels, the facilitation of membrane fusion and other phenomena of great biophysical interest. AA is a molecule that can appear as a membrane-soluble free fatty acid. Apart from its close relationship to inflammation, vasodilation and other biological processes, AA acts as a second messenger itself and can recruit -among others- certain protein kinase C isoforms.We developed different, GROMOS-based sets of descriptions for biologically relevant DAG isoforms and AA. We incorporated them into model phosphatidylcholine bilayer systems developed earlier [1], with or without the presence of cholesterol and at different concentrations. We subsequently employed Molecular Dynamics simulations of the mixed hydrated bilayer systems at the atomic level. The ensemble behavior of our systems was validated against experimental observations. Our results highlight the presence of modifications in the properties of the model bilayers by DAGs and AA in both a mechanical, bilayer patch-scale and a more local, atomic level; the latter in the form of organizational defects, e.g. voids.Our studies contribute in elucidating the underlying physical mechanisms of lipid-mediated signalling. Moreover, they provide clues in the context of determination of subtle biological distinction among different processes. Furthermore, they give rise to valid models for studying the interactions of lipid bilayers with certain lipid-responsive proteins by computational means.[1] Poger, D., and A. E. Mark. J. Chem. Theory Comput. (2009) 6:325.