Phosphatidic Acid Domains in Membranes: effect of Divalent Counterions
JORDI FARAUDO 1* and ALEX TRAVESSET 2
1 UNIVERSITAT AUTONOMA DE BARCELONA
2 IOWA STATE UNIVERSITY
* To whom correspondence should be addressed. E-mail: jordi.faraudo{at}uab.es.
Submitted on June 23, 2006
Revised on July 25, 2006
Accepted on 15 December 2006
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Abstract |
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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 µM to mM 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 paper, 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 counterions charges that exceeds the negative PA charge). We predict that a PA-rich domain undergoes a drastic reorganization when divalent cations reach µM 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.
Key Words:
Membranes, divalent ions, electrostatics, lipid domains, molecular dynamics simulations
