Mechanical Surface Waves Accompany Action Potential Propagation

Many studies have shown that a mechanical displacement of the axonal membrane accompanies the electrical pulse defining the Action Potential (AP). Despite a large and diverse body of experimental evidence, there is no theoretical consensus either for the physical basis of this mechanical wave nor its interdependence with the electrical signal. In this manuscript we present a model for these mechanical displacements as arising from the driving of surface wave modes in which potential energy is stored in elastic properties of the neuronal membrane and cytoskeleton while kinetic energy is carried by the axoplasmic fluid. In our model these surface waves are driven by the traveling wave of electrical depolarization that characterizes the AP, altering the compressive electrostatic forces across the membrane as it passes. This driving leads to co-propagating mechanical displacements, which we term Action Waves (AWs). Our model for these AWs allows us to predict, in terms of elastic constants, axon radius and axoplasmic density and viscosity, the shape of the AW that should accompany any traveling wave of voltage, including the AP predicted by the Hodgkin and Huxley (HH) equations. We show that our model makes predictions that are in agreement with results in experimental systems including the garfish olfactory nerve and the squid giant axon. We expect our model to serve as a framework for understanding the physical origins and possible functional roles of these AWs in neurobiology.Comment: 6 pages 3 figures + 2 page supplemen

Experimental observations of dynamic critical phenomena in a lipid membrane

Near a critical point, the time scale of thermally-induced fluctuations diverges in a manner determined by the dynamic universality class. Experiments have verified predicted 3D dynamic critical exponents in many systems, but similar experiments in 2D have been lacking for the case of conserved order parameter. Here we analyze time-dependent correlation functions of a quasi-2D lipid bilayer in water to show that its critical dynamics agree with a recently predicted universality class. In particular, the effective dynamic exponent $z_{\text{eff}}$ crosses over from $\sim 2$ to $\sim 3$ as the correlation length of fluctuations exceeds a hydrodynamic length set by the membrane and bulk viscosities.Comment: 5 pages, 3 figures and 2 additional pages of supplemen

Liquid general anesthetics lower critical temperatures in plasma membrane vesicles

A large and diverse array of small hydrophobic molecules induce general anesthesia. Their efficacy as anesthetics has been shown to correlate both with their affinity for a hydrophobic environment and with their potency in inhibiting certain ligand gated ion channels. Here we explore the effects that n-alcohols and other liquid anesthetics have on the two-dimensional miscibility critical point observed in cell derived giant plasma membrane vesicles (GPMVs). We show that anesthetics depress the critical temperature (Tc) of these GPMVs without strongly altering the ratio of the two liquid phases found below Tc. The magnitude of this affect is consistent across n-alcohols when their concentration is rescaled by the median anesthetic concentration (AC50) for tadpole anesthesia, but not when plotted against the overall concentration in solution. At AC50 we see a 4{\deg}C downward shift in Tc, much larger than is typically seen in the main chain transition at these anesthetic concentrations. GPMV miscibility critical temperatures are also lowered to a similar extent by propofol, phenylethanol, and isopropanol when added at anesthetic concentrations, but not by tetradecanol or 2,6 diterbutylphenol, two structural analogs of general anesthetics that are hydrophobic but have no anesthetic potency. We propose that liquid general anesthetics provide an experimental tool for lowering critical temperatures in plasma membranes of intact cells, which we predict will reduce lipid-mediated heterogeneity in a way that is complimentary to increasing or decreasing cholesterol. Also, several possible implications of our results are discussed in the context of current models of anesthetic action on ligand gated ion channels.Comment: 16 pages, 6 figure