Biomembranes are thin capacitors with the unique feature of displaying phase transitions in a physiologically relevant regime. We investigate the voltage and lateral pressure dependence of their ...capacitance close to their chain melting transition. Because the gel and the fluid membrane have different area and thickness, the capacitance of the two membrane phases is different. In the presence of external fields, charges exert forces that can influence the state of the membrane, thereby influencing the transition temperature. This phenomenon is called “electrostriction”. We show that this effect allows us to introduce a capacitive susceptibility that assumes a maximum in the melting transition with an associated excess charge. As a consequence, voltage regimes exist in which a small change in voltage can lead to a large uptake of charge and a large capacitive current. Furthermore, we consider electromechanical behavior such as pressure-induced changes in capacitance, and the application of such concepts in biology.
It has long been known that there is no measurable heat production associated with the nerve pulse. Rather, one finds that heat production is biphasic, and a heat release during the first phase of ...the action potential is followed by the reabsorption of a similar amount of heat during the second phase. We review the long history the measurement of heat production in nerves and provide a new analysis of these findings focusing on the thermodynamics of adiabatic and isentropic processes. We begin by considering adiabatic oscillations in gases, waves in layers, oscillations of springs and the reversible (or irreversible) charging and discharging of capacitors. We then apply these ideas to the heat signature of nerve pulses. Finally, we compare the temperature changes expected from the Hodgkin-Huxley model and the soliton theory for nerves. We demonstrate that heat production in nerves cannot be explained as an irreversible charging and discharging of a membrane capacitor as it is proposed in the Hodgkin-Huxley model. Instead, we conclude that it is consistent with an adiabatic pulse. However, if the nerve pulse is adiabatic, completely different physics is required to explain its features. Membrane processes must then be reversible and resemble the oscillation of springs more than resembling “a burning fuse of gunpowder” (quote A. L. Hodgkin). Theories acknowledging the adiabatic nature of the nerve pulse have recently been discussed by various authors. It forms the central core of the soliton model, which considers the nerve pulse as a localized sound pulse.
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.
On Soliton Propagation in Biomembranes and Nerves Heimburg, Thomas; Jackson, Andrew D.; Baym, Gordon A.
Proceedings of the National Academy of Sciences - PNAS,
07/2005, Letnik:
102, Številka:
28
Journal Article
Recenzirano
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The lipids of biological membranes and intact biomembranes display chain melting transitions close to temperatures of physiological interest. During this transition the heat capacity, volume and area ...compressibilities, and relaxation times all reach maxima. Compressibilities are thus nonlinear functions of temperature and pressure in the vicinity of the melting transition, and we show that this feature leads to the possibility of soliton propagation in such membranes. In particular, if the membrane state is above the melting transition solitons will involve changes in lipid state. We discuss solitons in the context of several striking properties of nerve membranes under the influence of the action potential, including mechanical dislocations and temperature changes.
The excitable fluid mosaic Heimburg, Thomas
Biochimica et biophysica acta. Biomembranes,
March 2023, 2023-03-00, 20230301, Letnik:
1865, Številka:
3
Journal Article
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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.11This article is dedicated to my late friend Luis A. Bagatolli (1966–2022).
•In the Fluid Mosaic Model, the membrane is a fluid layer in which proteins diffuse.•Deviations from the resting state lead to new layers of excitable phenomena.•Phase behavior, domains, rafts, and lipid-mediated rearrangements of proteins.•Temperature-dependent elastic behavior.•Adiabatic electromechanical pulses, pores and lipid ion channels.
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.
General anesthetics are known to cause depression of the freezing point of transitions in biomembranes. This is a consequence of ideal mixing of the anesthetic drugs in the membrane fluid phase and ...exclusion from the solid phase. Such a generic law provides physical justification of the famous Meyer-Overton rule. We show here that general anesthetics, barbiturates, and local anesthetics all display the same effect on melting transitions. Their effect is reversed by hydrostatic pressure. Thus, the thermodynamic behavior of local anesthetics is very similar to that of general anesthetics. We present a detailed thermodynamic analysis of heat capacity profiles of membranes in the presence of anesthetics. Using this analysis, we are able to describe experimentally observed calorimetric profiles and predict the anesthetic features of arbitrary molecules. In addition, we discuss the thermodynamic origin of the cutoff effect of long-chain alcohols and the additivity of the effect of general and local anesthetics.
Changes in the internal energy of lipids with temperature are related to both lipid volume and area changes. Close to the chain melting transition of lipid bilayers volume and enthalpy fluctuations ...generally follow proportional functions. This makes it possible to calculate the relationship between membrane excess heat capacity with lipid volume, area compressibility and the membrane bending modulus, if the area fluctuations of the two monolayers are assumed to be mainly decoupled. Thus, compressibility and elasticity display pronounced maxima at the chain melting transition. These maxima can also be related to pronounced minima of the sound velocity in the lipid transition range, which were found in ultrasonic experiments. In the present study heat capacity profiles and volume changes were obtained. The compressibilities and the bending modulus were then deduced from the specific heat. The relevance of these findings for structural transitions and for the curvature dependence of heat capacities is discussed.
Biological membranes are capacitors that can be charged by applying a field across the membrane. The charges on the capacitor exert a force on the membrane that leads to electrostriction, i.e. a ...thinning of the membrane. Since the force is quadratic in voltage, negative and positive voltage have an identical influence on the physics of symmetric membranes. However, this is not the case for a membrane with an asymmetry leading to a permanent electric polarization. Positive and negative voltages of identical magnitude lead to different properties. Such an asymmetry can originate from a lipid composition that is different on the two monolayers of the membrane, or from membrane curvature. The latter effect is called 'flexoelectricity'. As a consequence of permanent polarization, the membrane capacitor is discharged at a voltage different from zero. This leads to interesting electrical phenomena such as outward or inward rectification of membrane permeability. Here, we introduce a generalized theoretical framework, that treats capacitance, polarization, flexoelectricity, piezoelectricity and thermoelectricity in the same language. We show applications to electrostriction, membrane permeability and piezoelectricity and thermoelectricity close to melting transitions, where such effects are especially pronounced.
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