title: Regulation of the electric charge in phosphatidic acid domains.
abstract: Although a minor component of the lipidome, phosphatidic acid (PA) plays a crucial role in nearly all signaling pathways involving cell membranes, in part because of its variable electrical charge in response to environmental conditions. To investigate how charge is regulated in domains of PA, we applied surface-sensitive X-ray reflectivity and fluorescence near-total-reflection techniques to determine the binding of divalent ions (Ca(2+) at various pH values) to 1,2-dimyristoyl-sn-glycero-3-phosphate (DMPA) and to the simpler lipid dihexadecyl phosphate (DHDP) spread as monolayers at the air/water interface. We found that the protonation state of PA is controlled not only by the pK(a) and local pH but also by the strong affinity to PA driven by electrostatic correlations from divalent ions and the cooperative effect of the two dissociable protons, which dramatically enhance the surface charge. A precise theoretical model is presented providing a general framework to predict the protonation state of PA. Implications for recent experiments on charge regulation by hydrogen bonding and the role of pH in PA signaling are discussed in detail.
authors.affiliation: Ames Laboratory and Department of Physics and Astronomy, Iowa State University, Ames, Iowa 50011, USA.
authors.forename: Wenjie
authors.initials: W
authors.lastname: Wang
authors.forename: Nathaniel A
authors.initials: NA
authors.lastname: Anderson
authors.forename: Alex
authors.initials: A
authors.lastname: Travesset
authors.forename: David
authors.initials: D
authors.lastname: Vaknin
mesh_terms: D002118:Calcium / Q000737:chemistry; D006860:Hydrogen Bonding; D006863:Hydrogen-Ion Concentration; D007477:Ions / Q000737:chemistry; D008958:Models, Molecular; D010712:Phosphatidic Acids / Q000737:chemistry*; D011522:Protons; D055672:Static Electricity
chemical_list: D007477:Ions; D010712:Phosphatidic Acids; D011522:Protons; D002118:Calcium