Science
Living cells generate, respond to electricity Minute electric signals generated by cells may be important to reproduction and malignancy; electric pulses can aid cell fusion Living cells can generate minute electric signals and, under laboratory-controlled conditions, are sensitive and can be responsive to such signals coming from their environment. Particularly noteworthy is that electric signals can aid in the process of cell fusion whereby two cells of the same or of different types merge, forming a hybrid. These observations are among the highlights of research described by chemist Herbert A. Pohl, who is a member of the department of physics at Oklahoma State University, Stillwater. Pohl participated in a several-day symposium, sponsored by the Division of Colloid & Surface Chemistry, during the recent American Chemical Society national meeting in Las Vegas. Pohl's original observations date back about 15 years and revolve about a phenomenon called dialectrophoresis. This refers to the ability of uncharged materials to move when subjected to an electric field. Uncharged bodies, including living cells, can move under such circumstances because the electric field can polarize them, inducing a dipole that then
forces them to migrate like any other charged body in an electric field. Living cells, however, don't behave as simple polarizable blobs. Instead, they show variable sensitivity to applied fields, and typically each cell type has a characteristic spectrum of sensitivity that varies with radio frequency of the applied field, Pohl says. For example, this property can be used to separate cells in a mixture because different types will migrate only at certain applied radio frequencies, whereas others, remaining unpolarized, will stay still. These kinds of observations grew more interesting when "we took our binoculars and turned them around," Pohl continues. That is, instead of subjecting cells to externally applied electric fields and observing the effects, Pohl and his collaborators went looking for any electric signals the cells might be emitting. "The fields we're detecting from cells are extremely weak," he says. "They're so tiny, they're probably important only inside the cell. I don't think it's the secret of ESP or [nonsense] like that." Early observations of cellular electric signals were simple and served to prove the universality of the phenomenon. Cells were presented with powders having either a high or low dielectric constant. Under appropriately controlled conditions, most living cells selectively attract the polarizable, or "magic" as the Oklahoma group calls them, particles. One such typical particle of magic consists of barium titanate, BaTi03, powders. Based on how this powder
acts when tested in absence of cells, Pohl estimates the natural dipole about a cell's center as approximately 10~ 21 coulomb-meter, which corresponds to the displacement of about 108 electrons across an intracellular distance of 1 Â, he notes. It's important to keep in mind that it is not a static charge, but an oscillating one, Pohl says. A static dipole would be masked—literally but also figuratively damped out by the surrounding milieu of water, which supplies ions to neutralize any static charges. Thus, Pohl argues, a cell's charge is more akin to an ac than a dc circuit and is probably oscillating at a frequency of at least 5000 Hz. Such effects are observed for a wide variety of living cells, including bacteria, fungi, algae, and samples from mammalian tissues. "If we ask whether this observed field is a necessity or a frill, we speculate that it's a necessity," Pohl says. He reasons that its presence in such a variety of organisms, each presumably at a different stage of evolutionary sophistication and development, indicates a possibly fundamental role for this oscillatory electricity during the cellular life cycle. "I think it's important to reproduction," he says. Cellular reproduction, itself an important topic, has spillover importance for other vital topics, including malignancy. Logically, if a phenomenon such as natural radio frequency oscillations in cells is connected to their reproduction cycle under normal conditions, the phenomenon also might play some role
Micrographs from Zimmermann show two Vicia f aba cells fusing into one. At left, cells are aligned by dialectrophoresis. Next are the cells 10 seconds, then four minutes after application of a dc pulse. Picture at right shows cells fully fused 20
C&EN April 26, 1982
when the cycle becomes deranged during malignancy. This connection still is speculative, Pohl hastens to admit. Pohl also imagines ways in which these electrical phenomena may tie into specialized chemical reactions in cells. For example, some such reactions go through alternating cycles of ionic, then free-radical phases. It's possible that such cycles are tied to the DNA replication cycle. Applied radio frequency fields also can affect cells physically and directly. Thus, appropriate frequencies will cause cells to spin in resonance, Pohl says. Some of that spinning is due to neighboring cells inducing dipoles in one another, as his collaborator, Ulrich Zimmermann of Kernforschungsanlage, Julich, West Germany, has pointed out. But at least some spinning comes from an internally inducible dipole in cells, inasmuch as single cells can be made to spin, Pohl says. Possibly one of the most important contributions that Pohl and his collaborators have made is a remarkably efficient method for getting cells to fuse. The method probably rivals the
major one in use, which is dependent on polyethylene glycol. The alternative method, as currently developed and used by Pohl and his West German collaborators, depends on dialectrophoresis to line up cells along a platinum electrode. Typically, cells are subjected to a gentle ac field of about 5 volts at about 500 kHz. Then a pulse of about 15 volts dc for about 50 microseconds is applied. "It's easy to get 25% efficiency right away," Pohl says of the cell fusions that occur, adding: "Efficiencies are approaching 100%." He believes the process works so well by virtue of the high efficiency achieved in aligning the cells. Whatever the reason, the method could be valuable for the many scientists who undertake such fusions as a shortcut to obtaining new assortments of genes in cells. So far, the method has proved applicable to a wide variety of cells, including those of plant and animal origins. Pohl says that, until recently, his research has received support from the National Science Foundation. Currently, he says, his group is "having funding problems." D
Biotechnology's ties to academia assessed Two prominent figures in genetic engineering, one from academe and one from industry, gave generally upbeat analyses of the state of research in the field, the relationships between universities and the biotechnology industry, and the prospects for future growth of that industry to a symposium held recently in San Francisco. The symposium, which was sponsored by Beckman Instruments, drew about 180 participants from the biotechnology industry and companies thinking about becoming involved in biotechnology, as well as from universities and financial institutions. Two of the speakers, Arthur Kornberg, Nobel Laureate and professor of biochemistry at Stanford University, and Peter J. Farley, president of Cetus Corp., a biotechnology firm based in Berkeley, Calif., addressed themes similar to those addressed by the presidents of five major research universities at a conference last month (C&EN, April 5,
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April 26, 1982 C&EN
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