Membrane simulations mimicking acidic pH reveal increased thickness and negative curvature in a bilayer consisting of lysophosphatidylcholines and free fatty acids.
Phospholipids are key components of biological membranes and their lipolysis with phospholipase A(2) (PLA(2)) enzymes occurs in different cellular pH environments. Since no studies are available on the effect of pH on PLA(2)-modified phospholipid membranes, we performed 50-ns atomistic molecular dynamics simulations at three different pH conditions (pH 9.0, 7.5, and 5.5) using a fully PLA(2)-hydrolyzed phosphatidylcholine (PC) bilayer which consists solely of lysophosphatidylcholine and free fatty acid molecules. We found that a decrease in pH results in lateral squeezing of the membrane, i.e. in decreased surface area per headgroup. Thus, at the decreased pH, the lipid hydrocarbon chains had larger S(CD) order parameter values, and also enhanced membrane thickness, as seen in the electron density profiles across the membrane. From the lateral pressure profiles, we found that the values of spontaneous curvature of the two opposing monolayers became negative when the pH was decreased. At low pH, protonation of the free fatty acid headgroups reduces their mutual repulsion and accounts for the pH dependence of all the above-mentioned properties. The altered structural characteristics may significantly affect the overall surface properties of biomembranes in cellular vesicles, lipid droplets, and plasma lipoproteins, play an important role in membrane fission and fusion, and modify interactions between membrane lipids and the proteins embedded within them.
Lähdesmäki
Katariina
K
Wihuri Research Institute, Kalliolinnantie 4, FIN-00140 Helsinki, Finland. katariina.lahdesmaki@wri.fi
Ollila
O H Samuli
OH
Koivuniemi
Artturi
A
Kovanen
Petri T
PT
Hyvönen
Marja T
MT
D002462:Cell Membrane / Q000737:chemistry*; D005230:Fatty Acids, Nonesterified / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D008051:Lipid Bilayers / Q000737:chemistry*; D008244:Lysophosphatidylcholines / Q000737:chemistry*; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D015394:Molecular Structure
D005230:Fatty Acids, Nonesterified; D008051:Lipid Bilayers; D008244:Lysophosphatidylcholines