Thomas Heimburg

During the melting transition of dimyristoyl phosphatidylglycerol (DMPG), the order of the lipid chains and the three-dimensional, vesicular structural arrangement change simultaneously. These changes result in peculiar heat capacity profiles extended over a broad temperature range with seven $c_p$-maxima. Here, we present calorimetric, viscosity, and volume expansion coefficient data at various ionic strengths and charges. We propose a simple theory that explains the calorimetric data in terms of the coexistence of two membrane geometries, both of which can melt. During the transition, the equilibrium between these two geometries changes cooperatively. This equilibrium depends on the interactions between the membranes and the solvent, on the membrane's charge and the ionic strength of the buffer. Solvent interactions also contribute to the volume change of the membrane phases. Unlike uncharged membranes, we find that enthalpy changes are no longer proportional to volume changes. Therefore, the pressure dependence of the calorimetric profiles differs from that of uncharged membranes. Our theory explains the pressure dependence of calorimetric profiles qualitatively and quantitatively. Furthermore, we demonstrate that the same theory can be used to describe pretransition and ripple formation in phosphatidylcholines. A key takeaway from this article is that solvent molecules (e.g., H2O) are part of the membrane and, in the case of DMPG, water cannot be considered a separate phase.

The action potential is widely considered a purely electrical phenomenon. However, one also finds mechanical and thermal changes that can be observed experimentally. In particular, nerve membranes become thicker and axons contract. The spatial length of the action potential can be quite large, ranging from millimeters to many centimeters. This suggests to employ macroscopic thermodynamics methods to understand its properties. The pulse length is several orders of magnitude larger than the synaptic gap, larger than the distance of the nodes of Ranvier, and even larger than the size of many neurons such as pyramidal cells or brain stem motor neurons. Here, we review the mechanical changes in nerves, theoretical possibilities to explain them, and implications of a mechanical nerve pulse for the neuron and for the brain. In particular, the contraction of nerves gives rise to the possibility of fast mechanical synapses.

The Fluid Mosaic Model by Singer & Nicolson proposes that biological membranes consist of a fluid lipid layer into which integral proteins are embedded. The lipid membrane acts as a two-dimensional liquid in which the proteins can diffuse and interact. Until today, this view seems very reasonable and is the predominant picture in the literature. However, there exist broad melting transitions in biomembranes some 10-20 degrees below physiological temperatures that reach up to body temperature. Since they are found below body temperature, Singer & Nicolson did not pay any further attention to the melting process. But this is a valid view only as long as nothing happens. The transition temperature can be influenced by membrane tension, pH, ionic strength and other variables. Therefore, it is not generally correct that the physiological temperature is above this transition. The control over the membrane state by changing the intensive variables renders the membrane as a whole excitable. One expects phase behavior and domain formation that leads to protein sorting and changes in membrane function. Thus, the lipids become an active ingredient of the biological membrane. The melting transition affects the elastic constants of the membrane. This allows for the generation of propagating pulses in nerves and the formation of ion-channel-like pores in the lipid membranes. Here we show that on top of the fluid mosaic concept there exists a wealth of excitable phenomena that go beyond the original picture of Singer & Nicolson.

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.