4.1.2. Membrane interactions

Table 4.4 summarizes information relevant to electrical fields and their effects on biological membranes. Low-frequency alternating fields of the order of some hundred millivolts across the membrane can destroy it, as later described. The propagation of action potentials along nerves is initiated or interfered with by pulses or low-frequency potentials of roughly 10 mV across the membrane. Corresponding current densities and field-strength values in tissues and the medium external to the affected cell are of the order of 1 mA/cm² and 1 V/cm (Schwan, 1972; National Academy of Sciences, 1977; Schwan, 1971).

Table 4.4
Electrical-Field Effects On Membranes
Summary of various field effects on membranes (some established, some proposed). VM is the field-induced membrane potential; E, corresponding field strength in situ. E and VM are interrelated by VM = 1.5 ER (for spherical cells).

In recent years, some extraordinary sensitivities have been reported. Electrosensitive species, such as rays and sharks, detect fields of intensities as low as 0.1 V/cm. To achieve these sensitivities, they sample the field over considerable distances with the aid of special organs, the Ampullae Lorenzini, and operate over a small frequency range extending from dc to only a few hertz (National Academy of Sciences, 1977; Kalmijn, 1966). Some reports also indicate effects, due to ELF fields of the order of volts per centimeter in air, on timing responses and calcium efflux (Bawin and Adey, 1976; Gavalas-Medici and Day-Magdaleno, 1976). Corresponding in situ fields would be of the order of 0.1 V/cm, as listed in Table 4.4, and corresponding fields across membranes below 1 nV. It is, however, not yet obvious if the reported effects are caused by membrane processes; hence the reduction of external fields to in situ fields and then membrane potentials is not necessarily sensible. A more detailed discussion of this topic is given by Schwan (1971) and Bawin and Adey (1976) and the detailed report of the National Academy of Sciences-National Research Council on the biological effects of electric and magnetic fields (1977).
Microwave sensitivities of the order of 1 V/cm in situ have been frequently reported and correspond to external flux values of the order of 1 to 10 mW/cm². (See, for example, the recent text by Baranski and Czerski (1976).) Some suspect that these sensitivities correspond to direct interactions with the central nervous system. However, it is straightforward to translate in situ field levels to corresponding membrane potentials; and these are at levels of the order of 1 V or less, depending on microwave frequency, as discussed by Schwan (1971). The implications of these calculations have been challenged (Baranski and Czerski, 1976; Frey, 1971) by the argument that we do not yet know how the brain processes information. But Schwan finds it difficult to see how this rather general and no doubt valid statement pertains to his calculation of microwave-induced membrane potentials. At microwave frequencies, field-strength levels in membranes and in situ field levels are comparable within 1 order of magnitude. This must be so because in situ currents readily pass the membranes and enter the cell interior as well as the interior of subcellular organisms; moreover, dielectric constants of membranes (about 10) and cellular fluids (about 60 or less, depending on frequency) are similar in magnitude (Schwan, 1957). The membrane potential is, therefore, simply the product of in situ field strength and membrane thickness of about 10-6 cm. This simple argument does not depend on any particular model.
Although the microwave-induced membrane potential of about 1 V is comparable to and even higher than the perception level across the endepithelium of the Ampullae of Lorenzini, the high sensitivity of this endorgan is achieved only over a narrow bandpath range of some hertz. If microwave sensitivities existed over such narrow bandpath ranges, they would be hardly noticeable experimentally.
Also, the sensitivities of excitable cells to electric fields decrease rapidly as the electric stimulus is applied for time periods decreasingly short in comparison to the refractory period of the order of 1 ms. Hence quotation of reported low-frequency membrane sensitivities, as done by Frey (1971), carries no implication with regard to sensitivities claimed at microwave frequencies that correspond to time periods of the order of 1 ns, which is a million times smaller than the refractory period. More recently, Bawin and Adey (1977) have postulated that microwave fields may well be perceived if they are modulated with frequencies below 10 or 20 Hz. This would be possible in principle if induced in situ fields and if currents could be rectified with some degree of efficiency so that microwave fields would generate detectable low-frequency currents. No evidence for such a mechanism has been demonstrated so far at the membrane level.
In Table 4.5 available evidence on the threshold of biological excitation phenomena is summarized for various fields. In cardiology extended experience exists with pacemakers, and threshold values range about 0.1-10 mA/cm2, depending on electrode size and other parameters (Roy et al., 1976). In electrohypnosis, electrosleep, and electrical anesthesia, total currents applied are about 10-100 mA. Corresponding current densities in the brain may be estimated based on the work by Driscoll (1970). For a total 1-mA current applied to the head, internal brain current densities are of the order of 10 A/cm2 (Driscoll, 1970). Hence 10-100 mA of total current correspond to brain-tissue current densities of 0.1-1 mA/cm2 . Very extended work has been carried out on electrical hazards caused by low-frequency potentials applied to the human body (Schwan, 1972). The values quoted in Table 4.5 as thresholds for sensation, "let go," and fibrillation are all consistent with a current density of about 1 mA/cm 2. Thus membrane potentials in the millivolt range are consistent with the experience gained with pacemakers, effects on brain tissue, and electrical hazards.

Table 4.5
Biological Thresholds

4.1.3. Field-Generated Force Effects

Electric fields can directly interact with matter and create forces that can act on molecules as well as on cellular and larger structures. most of these interactions are reversible and do not necessarily have demonstrable biological effects. An example is the movement of ions in an ac field, which is inconsequential if the field is weak enough to prevent undue heating from molecular collisions (e.g., below about 1 V/cm, corresponding to 1 mA/cm 2 in a physiological medium). Another example is the orientation of polar macromolecules. For field-strength values of interest here, only a very partial, preferential orientation with the field results. Complete orientation and consequent dielectric saturation requires field strengths of thousands of volts per centimeter. (Changes of this magnitude do occur in membranes on depolarization, hence field-induced orientation and changes in orientation of membrane molecules appear possible. Corresponding tissue current densities would be in milliamperes per square centimeter.)
Electric fields can interact just as well with nonpolar cells and organelles in the absence of any net charge. These "ponderomotive" forces are well known and understood. Any system exposed to an electric field will tend to minimize its electric potential energy by appropriate rearrangement. This statement is equally true for dc and ac fields because the potential energy is a function of the square of the field strength. Inasmuch as the induced-dipole moment of a cell or large particle depends on both the square of field strength and the volume, it is not surprising that the threshold field to overcome thermal agitation is proportional to R -1.5, where R is the effective radius of the particle. Experimental evidence confirms the principle: threshold-field values for responses of 10-m cells are about 10 V/cm; but for 10-nm macromolecules, the fields are about 10 kV/cm--comparable with the fields needed for complete orientation--due to the existence of a typical dipole moment of about 10 or 100 Debyes.
Table 4.6 summarizes observed manifestations of field-generated forces. The field effects may manifest themselves as an orientation of particles in the direction of the field or perpendicular to it, or "pearl chain" formation (i.e., the alignment of particles in the field direction) may occur. This has long been considered a mysterious demonstration of microwave-induced biological effects. Cells can be deformed or destroyed with fields. In inhomogeneous electrical fields, the movement of cells can be affected.

Table 4.6. Mechanisms Caused By Field-Generated Forces


"Pearl chain" formation




Zimmerman et al. (1974) have observed the destruction of red cells and ghost formation. Neumann and Rosenheck (1972) studied the effects of fields on chromaffin vesicles. Friend et al. (1974) as well as Goodman et al. (1975, 1976) studied the effects of fields on fairly large cellular organisms. Orientation effects have been observed by Teixeirra-Pinto et al. (1960), Sher (1963), and Novak and Bentrup (1973). Pohl (1973) developed "dielectrophoresis" as a tool of separating cells in inhomogeneous fields, and Elul (1967) observed cell-destruction phenomena and cell-shape changes. No attempt is made here to summarize the total literature on this topic, and additional discussions have been presented elsewhere (Bawin and Adey, 1977; Schwan, 1977a). Some of these field-generated force effects can be very startling and dramatic, especially near the tip of small electrodes. Of a similar nature is the movement of magnetotactic bacteria, reported by Blakemore (1975), in magnetic fields of fairly low intensity. Apparently these bacteria are equipped with magnetic properties and are therefore significantly oriented by the magnetic field and motivated to move in the field direction.
Experimental and theoretical evidence indicates that pulsed fields cannot have greater effects than continuous fields of the same average power (Sher et al. , 1970) . Modulation is therefore not expected to have special effects.
Field forces due to the induced-dipole moment of the field have been listed as evidence of nonthermal action of electric fields on biologic systems. The effects, however, require fairly large field strengths, frequently above those that give rise to heating or stimulation of excitable tissues. The field forces also depend on the electric properties of the particle considered and its environment.
Sher (1968) has given a more detailed derivation of the dielectrophoretic force in lossy dielectric media, based in turn on a derivation of the potential electric energy of a lossy dielectric body given by Schwarz (1963).
All sorts of biological particles of different effective complex dielectric constants behave similarly in an electrolyte medium. Figure 4.5 illustrates this fact. Neumann and Rosenheck's (1972) results on chromaffin vesicles are combined with Sher's data (1963) on E. coli, erythrocytes, and silicon particles (full circles). The total material fits convincingly the solid line of slope -1.5 which is demanded by the theoretical requirement that particle volume must be inversely related to the square of the threshold-field strength mentioned here and discussed in greater detail elsewhere (Schwan and Sher, 1969).

Figure 4.5.
Threshold field-strength values as a function of particle size (Schwan, 1977a).
( ) Field-generated force effects; ( ) damage resulting from membrane breakdown at the quoted membrane potentials of 0.1 and 1 V; ( O ) results obtained with biological cells; and () data with silicone particles. The data fit the theoretical demand indicated by
( ) and appear to be insensitive to the dielectric properties of the particles.

The dashed curves in Figure 4.5 pertain to another model. The threshold of a cellular response or destruction is assumed to be reached when the induced membrane potential reaches the dielectric breakthrough level. This level may be in the range of 0.1 to 1 V across the membrane, corresponding to membrane field-strength levels from 100 kV/cm to 1,000,000 V/cm. The inverse relationship of the threshold-field level in the medium with the particle diameter follows from the equation VM = 1.5 ER (Table 4.4). The dashed curves in Figure 4.5 establish threshold particle relationships somewhat similar to those resulting from a consideration of field-generated forces. Hence separating biological effects due to field-generated forces from those due to induced high membrane potentials may at times be difficult.
In general, available evidence and present understanding indicate that significant effects with field-evoked forces require field-strength values above 1 V/cm in the medium unless cellular dimensions are well above 100 um.

4.1.4. Possibility of Weak Nonthermal Interactions

The considerations presented above do not suggest any weak nonthermal mechanism by which biological systems could react to low-intensity microwave fields. Fields of the order of a few kilovolts per centimeter are needed to orient long biopolymers, and probably still higher fields to excite internal vibrations or produce submolecular orientation. External fields acting on biopolymers must further overcome strong local fields, which are 1.5 kV/cm at a distance of 100 angstroms from a monovalent ion and 1.8 kV/cm at the same distance from a hemoglobin molecule. Microwave frequencies are well above those corresponding to significant rotational diffusion times, excluding orientational effects. Transmembrane potentials induced by typical nonthermal microwave fields are vanishingly small relative to potentials required for stimulation and compared with membrane noise. Field-induced force effects are unlikely to be significant on a single molecular or cellular level because the threshold field strengths necessary to overcome thermal disturbances are too high (Schwan, 1977a).
Some principles emerge, however, regarding possible mechanisms of weak microwave interaction, if such a concept exists. Field-force effects become more probable as the volume of the exposed particle increases (Schwan, 1977a). Transmembrane potentials become larger for a given in situ field strength as the cell size is increased. Finally, molecules can become significantly reoriented by the field if E kT (where is the dipole moment, E is the field strength, k is the Boltzman constant, and T is the absolute temperature); thus larger physical dimensions or larger permanent- or induced-dipole moments are more likely to respond to weak fields.
The large dimensions necessary for biological responses to weak microwave fields might be achieved by a cooperative reaction of a number of cells or macromolecules to the microwave stimulus, which increases the effective size of the structure and correspondingly reduces the threshold required for an effect. Bawin and Adey (1976) suggested that such cooperation might be induced in the counterions loosely bound near membrane surfaces which contain a loose framework of charged polysaccharides.
Froehlich (1973, 1975) suggested that giant dipole moments may be formed during enzyme substrate reactions and that the corresponding dielectric absorption processes might be highly resonant and nonlinear, and likely to channel energy into lower frequency modes of vibration. He also considered the membrane as a likely site of resonant electromagnetic (EM) interactions; and from the velocity of sound and the membrane thickness, he derived an estimate of the resonant frequencies to be of the order of 100 GHz. Acceleration and deceleration of a variety of biological responses that suggest resonances in the millimeter frequency range have been reported by Webb and Booth (1971), by Devyatkov (1974), and more recently by Grundier et al. (1977). But some of these studies have been criticized on technical grounds, and the Russian work (only summarized in 1974) has not yet been published in detail. Gandhi et al. (1979) conducted continuous dielectric spectroscopy measurements at millimeter-wave frequencies with no indication of any resonance processes. Also, on a variety of cellular processes they found no effects of millimeter-wave radiation that were not attributable to sample heating. But the resonance phenomena reported by Grundler et al. and postulated by Froehlich may only involve a minor fraction of the total cellular entity and thus not demonstrate itself strongly enough to be observed in the bulk dielectric data.

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Last modified: June 14, 1997
October 1986, USAF School of Aerospace Medicine, Aerospace Medical Division (AFSC), Brooks Air Force Base, TX 78235-5301