BIOPOLYMERS

VOL. 15 (1976)

Thermal and Electronic Contributions to Switching in Melanins

INTRODUCTION Melanin, an amorphous biopolymer, is found in uiuo in the skin, retina of the eye, inner ear, and several midbrain The recent discovery that this biopolymer responds dynamically to applied electric and acoustic fields has led to a new variety of possible biological roles in uiuo as well as the design of a potential new modality for treating melanoma, a malignant disease involving the melanin-producing cells."-5 The present study is directed toward a more complete understanding of the abrupt conductivity changes which, prior to their discovery in the melanins, were unknown in biological material^.^ Melanins respond a t a critical applied electrical field by changing their conductivity. The nature of the response depends upon the hydration and temperature of the sample and, to some extent, on the external circuitry. T h e response falls into two categories: threshold and memory switching. Threshold switching occurs when a sample cycles from an off (low conductivity) to an on (high conductivity) state a t a critical electric field and returns to the off state when the electric field is removed. Memory switching, on the other hand, refers to a sample which remains in the on state when the field is removed but can be restored to the off state by larger electric fields or currents. Both threshold and pseudomemory switching have been reported in melanins.".6 The memory state was found to return slowly to the off state; however, Culp et al.,6were unable to restore the on state electrically. This communication presents criteria which are particularly useful in separating thermal from electrical contributions. The memory state is reversible, destroyed by heating above 110°C, suggesting the existence of a true memory state.

EXPERIMENTAL CONDITIONS Synthetic melanins and melanosomes gently extracted from human malignant melanoma were prepared as previously reported.* A 2-mm diameter and 3-mm long cylindrical sample of melanin was compressed between carbon electrodes in a teflon holder whose temperature could be controlled between 24-200OC. Teflon was chosen since it is a good insulator and is relatively chemically inert. Furthermore, the elastic properties are ideal for containing melanins which become semifluid at very high hydrations. The thermal expansion of the holder over the temperature range did not appear to he a problem since the switching threshold is far more sensitive to hydration and temperature than to small changes in volume or geometry of the sample. A regulated power supply was used to apply voltage across the melanin sample and load resistor. The load resistor was chosen a t a low value (10 $2) to insure memory switching. Square waves with a rise time of lo-' sec and variable duration and amplitude were produced from the dc supply by a vibrating reed switch. The electrical history of the sample was recorded by photographing the voltage-current trace on a camera-equipped memory oscilloscope.

EXPERIMENTAL RESULTS Melanin in biological systems does not usually occur in a free form, but is polymerized into a structure (the melanosome) containing lipid and protein.* Synthetic melanin, however, can he polymerized without the lipid and protein fraction. This allows us t o investigate the purified materials first and then quantitate complications which arise as a result of incorporation of extraneous macromolecules. The response of melanin to an applied dc field depends on all of the available variables. The complications were reduced by first using samples a t a fixed (about 15%)hydration. At an applied field of 7.5 pV/A" across a 3-mm sample for example, pulse lengths less than 0.8 sec do not produce switching a t 24°C and 15%hydration. If a thermal contribution assists switching, heating the previously described sample should

2309 (C 1976 by John Wiley & Sons, Inc.

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BIOPOLYMERS VOL. 15 (1976) 3 ~ l O - pV/Ao l to 4.2pV/A0 G!

I

I

50 I00 Bulk Temperature- " C

I

I

I50

Fig. 1. The measured sample resistivity after the application of a 0.1-sec pulse exhibits switching only after a minimum temperature and electric field are exceeded. Above llO°C, however, the sample switches back off. This pattern can be repeated by cooling the sample and reheating. HYDRATION D E P E N D E N T M I N I M U M THERMAL ELECTRIC B I A S 20pV/A0

t

E l e c t r i c Field Strength

Fig. 2. The minimum temperature and electric field required to produce the on state depend on the hydration as illustrated. The on state can only be produced within the shaded region for a 0.1-sec pulse. Attempts to switch these materials outside the appropriate region for the pulse duration and type of melanin will be unsuccessful. It is essential, therefore, to obtain this type of plot for materials which have not been previously investigated. initiate switching. In fact, at 24OC and 15%hydration, a 0.1-sec pulse width did not produce switching even with a pulse height of 20 pV/Ao; however, at 6OoC the same will switch with a 5 pV/A", 0.1-sec applied pulse. The results for a 0.1-sec pulse and 15%hydration are summarized in Figure 1. Although a family of such curves can be generated for different pulse lengths, the results at a fixed value provide the information we require. If the hydration of the sample is varied, the minimum thermal electric bias is obtained (see Fig. 2).

COMMUNICATIONS T O T H E EDITOR

231 1

T A B L E 1” %

Threshold Voltage

Synthetic Melanins L-Dopa

1 10 20 30

(V) 135 120 100

Tumor Melanosomes

1 10 30

250 200 150

Hydration

Threshold Temperature (“C) -

57 40 24 75 75 24

a Increasing t h e hydration of t h e bulk sample lowers t h e threshold temperature a n d electric field required for producing t h e “ o n ” state b u t does n o t change t h e temperature (110°C) a t which t h e samples switch back off. T h e melanosomes were interrogated u p to 75°C. However, denaturation of t h e samples prevented measurements a t 1 1 0 ° C .

DISCUSSION AND CONCLUSIONS The threshold electric field and threshold temperature required to activate memory switehing for a 0.1-sec pulse are tabulated in Table I for synthetic melanin and melanosomes. The data in Table I are obtained by starting with a melanin sample a t a fixed hydration and defining the voltage required to activate switching. Below a critical temperature the sample will not switch with the electric fields indicated. Between the critical temperature (where the melanin is first capable of switching on a t the chosen field strength) and approximately ll0OC (where it switches off) the samples switch a t almost the same applied field. For synthetic melanin, the switched sample will return to the off (or unswitched) condition at 110-c, and the sample can be cooled and recycled as often as desired. The melanosomes show essentially the same results as purified melanins for the initial critical temperature required to activate switching; however, the melanosomes degrade below 110°C and thus the off state could not be reached by heating. The critical temperature and applied field have been discussed since they are the easiest external variables to control. The current and power are also obviously of interest. In an earlier study the repeated switching of a given sample, a t a fixed temperature and hydration, caused the threshold voltage to vary more than the threshold current. This suggests that these are current-operated devices; however, neither the current nor the voltage is a linear function of the sample width. The threshold power required varied almost linearly with the sample width for samples near the minimum (see Fig. 2). Thus, neither the hydration nor temperature nor current nor applied field, nor power alone is sufficient to assure switching. One must specify the temperature, the hydration, and either the applied field, current, or power. Since the voltage is usually the easiest variable to hold constant, we have chosen it first to characterize the material. The melanins offer a unique experimental system for the development of a working concept of biological semiconductivity, which contrasts markedly with classical crystalline semiconductivity. The melanins are capable of absorbing other molecules and expressing this interaction by a conductivity change of as much as ten orders of magnitude. Due to the stability of the melanins, a class of compounds including water, dimethylsulfoxide, formamide, and methyl alcohol have been found to modify reversibly the conductivity. The increase in conductivity reaches a limiting value which monotonically increases with the dielectric constant of the absorbed molecule. Furthermore, electron spin resonance studies with these particular compounds have indicated that the electron spin resonance is negatively correlated with conductivity (M. Eisner and S. C. Moss, private communication). The higher the static dielectric constant, the higher the conductivity and the lower the electron spin resonance (in

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BIOPOLYMERS VOL. 15 (1976)

terms of spins per mass of melanin a t a given temperature, mass of guest material absorbed, pH, and light exposure.) These experimental observations suggest to us that the melanins may contain a large density of localized states a t the Fermi level. As previously s u g g e ~ t e din ~ .dry ~ melanins many of these localized states are singly occupied leading to the high electron spin resonance. As the molecules are absorbed by the melanin, the localized states may spread out and overlap, pairing off spins and increasing conductivity. Some absorbed molecules will be expected to break this pattern. The electron spin resonance is also pH dependent. Even weak acids or bases can change the proton distribution and destroy the simple negative correlation described. Furthermore, benzene has been found to have no effect on conductivity. This is expected from its low static dielectric constant; however, it is capable of reducing the electron spin resonance. The possibility of developing equivalence classes of compounds which have particular types of effects on melanin is potentially a powerful experimental technique for probing the physical interactions which are present. In fact, several classes of melanin-associating compounds have already been discussed as biologically relevant. Lindquest et al. have suggested that the melanin-binding drugs are specific for inducing toxicity in uiuo in melanized cells. Proctor et al. have suggested a triad of cylinical symptoms, psychosis, diskinesia, and pigmentation abnormalities involving the chronic presence of charge-transfer agents in man. Experiments now in progress suggest that these compounds do alter the physical state of the melanins. Useful data can be obtained in switching experiments involving melanins which are purposely altered by these compounds. This work was supported in part by Grant CA-17891 from the U. S. Public Health Service and Contract A7-(40-1)-2832 from the Energy Research and Development Administration.

References 1. Cotzias, G. C., Papavasiliou, P. S., Van Woert, M. H. & Sakamoto, A. (1964) Fed. R o c . 23,713-717. 2. Lindquist, N. G. (1973) ACIA Radiol. (Suppl. 325), 1-92. 3. McGinness, J. E. & Proctor, P. H. (1973) J. Theor. Biol. 39 677-678. 4. McGinness, J. E., Corry, P. M. & Proctor, P. H. (1975) Year Book of Cancer, Year Book Medical Publishers, Chicago, Ill., pp. 521-522. 5. McGinness, J. E., Corry, P. M. & Proctor, P. H. (1974) Science 183,853-855. 6. Culp, C. H., Eckels, D. E. & Sidles, P. H. (1975) J.Appl. Phys. 46,3658-3659. 7. Van Woert, M. H., Prasad, K. N. & Borg, D. C. (1967) J . Neurochem. 14,707-715. 8. Mizutani, U., Massalski, T. B., McGinness, J. E. & Corry, P. M. (1976) Nature 259, 505-507. 9. McGinness, J. E. (1972) Science 177,896-897. 10. Proctor, P. (1974) J. Theor. Biol. 48,19-23.

School of Engineering North Carolina A&T State University Greensboro, North Carolina 27411

JURIFILATOVS

Department of Physics The University of Texas System Cancer Center M. D. Anderson Hospital and Tumor Institute Houston, Texas 77030

JOHN MCGINNESS PETERCORRY

Received January 26,1976 Returned for revision March 15, 1976 Accepted May 10,1976

Thermal and electronic contributions to switching in melanins.

BIOPOLYMERS VOL. 15 (1976) Thermal and Electronic Contributions to Switching in Melanins INTRODUCTION Melanin, an amorphous biopolymer, is found in...
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