Local micro-partition coefficients govern solute permeability of cholesterol-containing membranes
Sprache des Vortragstitels:
Englisch
Original Tagungtitel:
Biophysical Society 57th Annual Meeting: February 2-6, 2013
Sprache des Tagungstitel:
Englisch
Original Kurzfassung:
Local micro-partition coefficients govern solute permeability of cholesterol-containing membranes
Florian Zocher 1, Christian L. Wennberg 2, David van der Spoel 2, Peter Pohl 1,*, Jochen S. Hub 3
1Institut für Biophysik, Johannes Kepler Universität, Gruberstraße 40, 4020 Linz, Austria,
2Department of Cell and Molecular Biology, Uppsala University, Box 596, SE-75124 Uppsala, Sweden
3Institute for Microbiology and Genetics, Georg-August-University Göttingen, Justus-von-Liebig-Weg 11, 37077 Göttingen, Germany
Abstract
It has long been recognized that the effects of both lipid structure and solute size on solute membrane permeability Pm are at odds with the solubility diffusion model, in which both the partition coefficient K and the transverse diffusion coefficient D are assumed to be independent of solute penetration depth. As we show here, cholesterol may increase the apparent discrepancy between model and experiment, as Pm of our model solute tetraethylammonium (TEA) increased upon the addition of cholesterol. Using scanning electrochemical microscopy, we observed the steady state TEA flux across planar lipid bilayers from monounsaturated phospholipids. The flux was maximal at 20 mol % cholesterol concentration. At 40 mol % the flux-accelerating cholesterol effect vanished. According to molecular dynamics simulations, cholesterol did not take effect in altering D. Instead, cholesterol increased K in the head group region that forms the flux-limiting barrier for TEA at low cholesterol content. Structurally, cholesterol increases the distance between the head groups, thereby facilitating the intrusion of the apolar TEA into the polar head group region. At higher concentrations, cholesterol decreased K in the tail region through tighter packing of the lipid tails. For small hydrophobic molecules, K scarcely depends on the cholesterol content as does Pm, which is obtained by integrating over all penetration depth-dependent 1/(DK).