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.

It is known that lipid membranes become permeable in their melting regime. In microscopic conductance measurements on black lipid membranes one finds that conduction takes place via quantized events closely resembling those reported for protein ion channels. Here, we present data of ion currents through black lipid membranes in the presence and absence of the anesthetics octanol and ethanol, and compare them to a statistical thermodynamics model using parameters that are obtained from experimental calorimetric data. The conductance steps in pure lipid membrane suggest aqueous pores with the size of approximately one lipid cross-section. We model the permeability by assuming empty sites of the size of one lipid. We find that pore formation in the melting transition regime is facilitated by the increase of the lateral compressibility that expresses itself in the area fluctuations. Thus, pore formation is related to critical opalescence in two dimensions. Anesthetics alter the permeability by affecting the thermodynamic state of the membrane and by shifting the heat capacity profiles. † K. Wodzinska and A.Blicher contributed equally to this work.

It is well known that at the gel-liquid phase transition temperature a lipid bilayer membrane exhibits an increased ion permeability. We analyze the quantized currents in which the increased permeability presents itself. The open time histogram shows a "-3/2" power law which implies an open-closed transition rate that decreases like k(t) ∝ t −1 as time evolves. We propose a "pore freezing" model to explain the observations. We discuss how this model also leads to the 1/f α noise that is commonly observed in currents across biological and artificial membranes.

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