Timothy E. Vaughan

Biological sensing of small field differences by magnetically sensitive chemical reactions.

There is evidence that animals can detect small changes in the Earths magnetic field by two distinct mechanisms, one using the mineral magnetite as the primary sensor and one using magnetically sensitive chemical reactions. Magnetite responds by physically twisting, or even reorienting the whole organism in the case of some bacteria, but the magnetic dipoles of individual molecules are too small to respond in the same way. Here we assess whether reactions whose rates are affected by the orientation of reactants in magnetic fields could form the basis of a biological compass. We use a general model, incorporating biological components and design criteria, to calculate realistic constraints for such a compass. This model compares a chemical signal produced owing to magnetic field effects with stochastic noise and with changes due to physiological temperature variation. Our analysis shows that a chemically based biological compass is feasible with its size, for any given detection limit, being dependent on the magnetic sensitivity of the rate constant of the chemical reaction.

Theoretical limits on the threshold for the response of long cells to weak extremely low frequency electric fields due to ionic and molecular flux rectification.

Understanding exposure thresholds for the response of biological systems to extremely low frequency (ELF) electric and magnetic fields is a fundamental problem of long-standing interest. We consider a two-state model for voltage-gated channels in the membrane of an isolated elongated cell (Lcell = 1 mm; rcell = 25 micron) and use a previously described process of ionic and molecular flux rectification to set lower bounds for a threshold exposure. A key assumption is that it is the ability of weak physical fields to alter biochemistry that is limiting, not the ability of a small number of molecules to alter biological systems. Moreover, molecular shot noise, not thermal voltage noise, is the basis of threshold estimates. Models with and without stochastic resonance are used, with a long exposure time, texp = 10(4) s. We also determined the dependence of the threshold on the basal transport rate. By considering both spherical and elongated cells, we find that the lowest bound for the threshold is Emin approximately 9 x 10(-3) V m-1 (9 x 10(-5) V cm-1). Using a conservative value for the loop radius rloop = 0.3 m for induced current, the corresponding lower bound in the human body for a magnetic field exposure is Bmin approximately 6 x 10(-4) T (6 G). Unless large, organized, and electrically amplifying multicellular systems such as the ampullae of Lorenzini of elasmobranch fish are involved, these results strongly suggest that the biophysical mechanism of voltage-gated macromolecules in the membranes of cells can be ruled out as a basis of possible effects of weak ELF electric and magnetic fields in humans.

Biological Effects Due to Weak Electric and Magnetic Fields: The Temperature Variation Threshold

A large number of epidemiological and experimental studies suggest that prolonged (>100 s) weak 50-60-Hz electric and magnetic field (EMF) exposures may cause biological effects(NIEHS Working Group, NIH, 1998; Bersani, 1999). We show, however, that for typical temperature sensitivities of biochemical processes, realistic temperature variations during long exposures raise the threshold exposure by two to three orders of magnitude over a fundamental value, independent of the biophysical coupling mechanism. Temperature variations have been omitted in previous theoretical analyses of possible weak field effects, particularly stochastic resonance (Bezrukov and Vodyanoy 1997a. Nature. 385:319-321; Astumian et al., 1997 Nature. 338:632-633; Bezrukov and Vodyanoy, 1997b. Nature. 338:663; Dykman and McClintock, 1998. Nature. 391:344; McClintock, 1998;. Gammaitoni et al., 1998. Rev. Mod. Phys. 70:223-287). Although sensory systems usually respond to much shorter (approximately 1 s) exposures and can approach fundamental limits (Bialek, 1987 Annu. Rev. Biophys. Biophys. Chem. 16:455-468; Adair et al, 1998. Chaos. 8:576-587), our results significantly decrease the plausibility of effects for nonsensory biological systems due to prolonged, weak-field exposures.

Spatially constrained skin electroporation with sodium thiosulfate and urea creates transdermal microconduits

Controlled transport of molecules through the skins main barrier, the stratum corneum (SC), is a long standing goal of transdermal drug delivery. Traditional, needle-based injection provides delivery of almost any water soluble compound, by creating a single large aqueous pathway in the form of the hollow core of a needle, through which drug is delivered by pressure-driven flow. We extend previous work to show that SC-spanning microconduits (here with diameters of about 200 microm) can be created in vivo by skin electroporation and low-toxicity, keratolytic molecules (here sodium thiosulfate and urea). A single microconduit in isolated SC can support volumetric flow of the order of 0.01 ml s(-1) by a pressure difference of only 0.01 atm (about 10(2) Pa), demonstrating that the SC barrier has been essentially eliminated within this microscopic area.

Spatially constrained localized transport regions due to skin electroporation.

Rapid, controlled molecular transport across human skin is of great interest for transdermal drug delivery and minimally invasive chemical sensing. Short, high-voltage pulses have been shown previously to create localized transport regions in the skin. Here, we show that these regions can be constrained to occur at specific sites using electrically insulating masks that restrict the field lines. The increase in total ionic and molecular transport per area was comparable to the levels observed in unconstrained electroporation of human skin. Constraining the area of intervention to encompass small areas of interest, a primary feature in the design of microdevices for transdermal drug delivery, can provide the same levels of flux as the unconstrained case.

Molecular change due to biomagnetic stimulation and transient magnetic fields: mechanical interference constraints on possible effects by cell membrane pore creation via magnetic particles

Abstract Possible human health hazards due to biomagnetic stimulation and other transient magnetic fields are assessed theoretically by considering magnetic field pulses that might create metastable cell membrane pores via interaction with membrane-attached magnetic particles. Such pores could lead to molecular changes sufficient to alter biochemical processes by admitting extracellular molecules that ordinarily cannot enter the cytosol, and can generate a molecular influx burst which satisfies a molecular shot noise constraint. Sources of competing molecular changes are considered. Possible pore creation due to normally encountered accelerations is usually insignificant. However, mechanical interference arising from membrane openings by tissue strain in naturally moving tissues is expected to lead to more severe competing molecular changes for most cells; only cells of bone-encased tissues (marrow and brain) remain as candidates. Such mechanical interference is also relevant to any other biophysical mechanism that couples molecular change to electric or magnetic fields by cellular deformation.

A Theoretical Model for Cell Electroporation: Quantitative Description of Electrical Behavior

A large number of studies have been performed on the application of electric field pulses to membranes. These studies have almost universally shown that reversible electrical breakdown and significant molecular uptake occur if the transmembrane voltage reaches about 0.5–1.0 V.1–3

Recent Advances in Skin Electroporation: Mechanism and Efficacy

Rapid, controlled molecular transport across human skin is of great interest for transdermal drug delivery and noninvasive chemical sensing. The main barrier is the stratum corneum (SC), which can be described by a “brick wall” model in which the dead, hydrated corneocytes are the bricks, and the surrounding multilamellar lipid bilayer membranes are the mortar. Small lipid-soluble molecules can partition into the SC, and then diffuse across the lipid bilayer membranes, but water soluble molecules, particularly charged molecules, cannot penetrate significantly by this route. Pre-existing aqueous pathways associated with the skin’s appendages (sweat gland duets and hair follicles) admit water soluble molecules, and are believed to provide one major route for iontophoresis, in which low voltages are used to move ions and molecules across the skin. However, iontophoresis often provides molecular fluxes which are smaller than needed.

Injury Associated with High Voltage Pulsing for Transdermal Drug Delivery

High voltage (HV) transdermal pulses have been hypothesized to cause electroporation within the stratum corneum (SC) of the skin, and are under investigation for transdermal drug delivery and analyte extraction for non-invasive sensing.1–14 Possible side effects related to tissue injury must therefore be considered, and found acceptable for the benefit derived. Here we consider the theoretical basis for some of the likely sources of injury, and briefly review the findings of experimental studies.

Cell Membrane Pore Creation via Magnetic Particles: Biomagnetic Stimulation and Transient Magnetic Fields

Controversy over possible health hazards from environmental electric and magnetic fields (EMF) is partly due to the lack of an established biophysical mechanism. Such a mechanism is required to explain how physical fields are coupled to the biology, in order to produce a biochemical change. In other words, the mechanism must specifically and quantitatively account for a causal molecular change caused by EMF.