Non-linear Conductance, Rectification, and Mechanosensitive Channel Formation of Lipid Membranes

Abstract

There is mounting evidence that lipid bilayers display conductive properties. However, when interpreting the electrical response of biological membranes to voltage changes, they are commonly considered as inert insulators. Lipid bilayers under voltage-clamp conditions display current traces with discrete conduction-steps, which are indistinguishable from those attributed to the presence of protein channels. In current-voltage (I-V) plots they may also display outward rectification, i.e., voltage-gating. Surprisingly, this has even been observed in chemically symmetric lipid bilayers. Here, we investigate this phenomenon using a theoretical framework that models the electrostrictive effect of voltage on lipid membranes in the presence of a spontaneous polarization, which can be recognized by a voltage offset in electrical measurements. It can arise from an asymmetry of the membrane, for example from a non-zero spontaneous curvature of the membrane. This curvature can be caused by voltage via the flexoelectric effect, or by hydrostatic pressure differences across the membrane. Here, we describe I-V relations for lipid membranes formed at the tip of patch pipettes situated close to an aqueous surface. We measured at different depths relative to air/water surface, resulting in different pressure gradients across the membrane. Both linear and non-linear I-V profiles were observed. Non-linear conduction consistently takes the form of outward rectified currents. We explain the conductance properties by two mechanisms: One leak current with constant conductance without pores, and a second process that is due to voltage-gated pore opening correlating with the appearance of channel-like conduction steps. In some instances, these non-linear I-V relations display a voltage regime in which dI/dV is negative. This has also been previously observed in the presence of sodium channels. Experiments at different depths reveal channel formation that depends on pressure gradients. Therefore, we find that the channels in the lipid membrane are both voltage-gated and mechanosensitive. We also report measurements on black lipid membranes that also display rectification. In contrast to the patch experiments they are always symmetric and do not display a voltage offset.

Bilayer Lipid Membrane as Memcapacitance: Capacitance–Voltage Pinched Hysteresis and Negative Insertion Conductance

“…In this voltage range, the conductance sharply increases and, possibly, the coefficient of nonlinearity of the capacitance decreases. For better agreement between the experimental and theoretical curves, we take into account the possibility of the appearance of nonlinear conductance at high voltages [ 27 , 28 ]. We approximate the conductance current by a ninth-degree polynomial (3) with the parameter γ = 0.5 10 −18 nS/mV 8 .…”

“…The third branch represents ionic currents through the membrane, which arise when the ionic permeability of the membranes increases. In order to better agree with the experimental data, this model provides the possibility of the appearance of nonlinear conductance at high membrane voltages, which was observed in studies of both artificial [ 27 ] and cell membranes [ 28 ]. Following [ 28 ], where the current–voltage profile of the cell was represented by a 9th order polynomial, we represent the ion current through the membrane as where g is the linear conductance of the membrane, γ is an empirical coefficient of nonlinearity of membrane conductance.…”

Bio-Mimicking, Electrical Excitability Phenomena Associated With Synthetic Macromolecular Systems: A Brief Review With Connections to the Cytoskeleton and Membraneless Organelles

“…When using the patch-clamp technique, one can record unitary opening and closing events of ionic currents in the pA scale. Less well known is that similar, square-wave current transients can also be seen with pure lipid membranes ( Blicher and Heimburg, 2013 ; Zecchi and Heimburg, 2020 ). Figure 1 depicts one example of this type of current trace, which appear indistinguishable from those recorded in lipid membranes containing proteins, either from synthetic preparations or from living cells.…”

“…Possible mechanisms for pore formation in pure lipid membranes and details of experimental conditions have been discussed in detail elsewhere ( Heimburg, 2010 ; Blicher and Heimburg, 2013 ). Although the formation of pores of various sizes (subconductances) occur in a stochastic way, it has also been proposed that the application of transmembrane voltage may favor the formation of pores with a specific radius ( Glaser et al, 1988 ; Zecchi and Heimburg, 2020 ).…”

The thermodynamic soliton theory of the nervous impulse and possible medical implications

“…This happens in particular close to the melting transitions (74)(75)(76)(77)(78)(79) that are the central requirement for the creation of solitons in nerves. These events are influenced by changes in temperature, calcium concentration, membrane tension, and voltage (see (79) and references therein, (73,80)) and pH (81,82). In particular, they are voltage-gated, i.e., the open probability of the channels increases with increasing voltage (see Fig.…”