Phosphatidic acid domains in membranes: Effect of divalent counterions

TitlePhosphatidic acid domains in membranes: Effect of divalent counterions
Publication TypeJournal Article
Year of Publication2007
AuthorsFaraudo J, Travesset A
Journal TitleBiophysical Journal
Volume92
Pages2806-2818
Date PublishedApr
Type of ArticleArticle
ISBN Number0006-3495
Accession NumberISI:000245164000019
Keywordsaqueous-solutions, CA2+ BINDING, charged interfaces, DIPALMITOYLPHOSPHATIDYLSERINE, ELECTROSTATICS, LIPID-BILAYERS, LYSOPHOSPHATIDIC ACID, MOLECULAR-DYNAMICS SIMULATION, phospholipid-membranes, water
Abstract

Phosphatidic acid (PA) is emerging as a key phospholipid in a wide range of biological processes such as signal transduction, secretion, or membrane fusion. In most cases, the biological functionality of PA is associated with the presence of micromolar to millimolar calcium concentrations. It has been argued that PA can create defects in the packing of lipids in membranes due to lateral phase separation by divalent ions, which in turn aggregate proteins with high affinity for PA. In this article, we present a detailed investigation of the properties of PA domains in the presence of divalent ions by a combination of molecular dynamics simulations and theoretical methods. Our results show that PA is extremely effective in binding divalent ions through its oxygen atoms, with a broad distribution of binding constants and exhibiting the phenomenon of charge inversion (a total number of bound counterion charges that exceeds the negative PA charge). We predict that a PA-rich domain undergoes a drastic reorganization when divalent cations reach micromolar concentrations (i.e., typical physiological conditions), as PA lipids become doubly charged by releasing their protons. We also present a detailed investigation of the properties of interfacial water, which determine the binding of proteins or other molecules. We conclude with a discussion of the implications of our results in the context of recent experimental studies in model systems and in real cells.

DOI10.1529/biophysj.106.092015
Alternate JournalBiophys. J.