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.

In this article we compare electrical conductance events from single channel recordings of three TRP channel proteins (TRPA1, TRPM2 and TRPM8) expressed in human embryonic kidney cells with channel events recorded on synthetic lipid membranes close to melting transitions. Ion channels from the TRP family are involved in a variety of sensory processes including thermo- and mechano-reception. Synthetic lipid membranes close to phase transitions display channel-like events that respond to stimuli related to changes in intensive thermodynamic variables such as pressure and temperature. TRP channel activity is characterized by typical patterns of current events dependent on the type of protein expressed. Synthetic lipid bilayers show a wide spectrum of electrical phenomena that are considered typical for the activity of protein ion channels. We find unitary currents, burst behavior, flickering, multistep-conductances, and spikes behavior in both preparations. Moreover, we report conductances and lifetimes for lipid channels as described for protein channels. Non-linear and asymmetric current-voltage relationships are seen in both systems. Without further knowledge of the recording conditions, no easy decision can be made whether short current traces originate from a channel protein or from a pure lipid membrane.

Synthetic lipid membranes can display channel-like ion conduction events even in the absence of proteins. We show here that these events are voltage-gated with a quadratic voltage dependence as expected from electrostatic theory of capacitors. To this end, we recorded channel traces and current histograms in patch-experiments on lipid membranes. We derived a theoretical current-voltage relationship for pores in lipid membranes that describes the experimental data very well when assuming an asymmetric membrane. We determined the equilibrium constant between closed and open state and the open probability as a function of voltage. The voltage-dependence of the lipid pores is found comparable to that of protein channels. Lifetime distributions of open and closed events indicate that the channel open distribution does not follow exponential statistics but rather power law behavior for long open times.

Synthetic lipid membranes can display channel-like ion conduction events even in the absence of proteins. We recorded channel traces and current histograms in patch-experiments on synthetic lipid membranes. We show that these events are voltage-gated with voltage dependence as expected from electrostatic theory of capacitors. The voltage-dependence of the lipid channel open probability was found comparable to that of protein channels. We find rectified currentvoltage relationships very similar to those of TRP channels. We derived a theoretical IV-profile that well describes the experimental data, but also those of some proteins. This suggests that the electrostatic theory of capacitors has the potential to contribute to the understanding of channel gating.