The temperature dependence of lipid membrane permeability, its quantized nature, and the influence of anesthetics.
We investigate the permeability of lipid membranes for fluorescence dyes and ions. We find that permeability reaches a maximum close to the chain melting transition of the membranes. Close to transitions, fluctuations in area and compressibility are high, leading to an increased likelihood of spontaneous lipid pore formation. Fluorescence correlation spectroscopy reveals the permeability for rhodamine dyes across 100-nm vesicles. Using fluorescence correlation spectroscopy, we find that the permeability of vesicle membranes for fluorescence dyes is within error proportional to the excess heat capacity. To estimate defect size we measure the conductance of solvent-free planar lipid bilayer. Microscopically, we show that permeation events appear as quantized current events very similar to those reported for channel proteins. Further, we demonstrate that anesthetics lead to a change in membrane permeability that can be predicted from their effect on heat capacity profiles. Depending on temperature, the permeability can be enhanced or reduced. We demonstrate that anesthetics decrease channel conductance and ultimately lead to blocking of the lipid pores in experiments performed at or above the chain melting transition. Our data suggest that the macroscopic increase in permeability close to transitions and microscopic lipid ion channel formation are the same physical process.
Blicher
Andreas
A
Niels Bohr Institute, University of Copenhagen, Copenhagen, Denmark.
Wodzinska
Katarzyna
K
Fidorra
Matthias
M
Winterhalter
Mathias
M
Heimburg
Thomas
T
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry; D000465:Algorithms; D000777:Anesthetics / Q000494:pharmacology*; D002151:Calorimetry; D002463:Cell Membrane Permeability / Q000187:drug effects* / Q000502:physiology*; D005456:Fluorescent Dyes; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D007473:Ion Channels / Q000737:chemistry / Q000378:metabolism; D007477:Ions; D007700:Kinetics; D008051:Lipid Bilayers / Q000737:chemistry; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D010713:Phosphatidylcholines / Q000737:chemistry; D010715:Phosphatidylglycerols / Q000737:chemistry; D013057:Spectrum Analysis; D013696:Temperature
D000777:Anesthetics; D005456:Fluorescent Dyes; D007473:Ion Channels; D007477:Ions; D008051:Lipid Bilayers; D010713:Phosphatidylcholines; D010715:Phosphatidylglycerols; D015060:1,2-Dipalmitoylphosphatidylcholine; C017251:1,2-oleoylphosphatidylcholine; C030345:1,2-dipalmitoylphosphatidylglycerol