74
Electromagnetic Fields in Biological Systems
observable effect was the rapid increase of electrical conductivity. The conductivity
change was attributed to pore formation in the lipid bilayer membrane. Further evidence for chemical transport through membranes involved experiments with red blood
cells (Sukhorukov, Mussauer, and Zimmermann 1998; Kinosita and Tsong 1977; Teissie
and Tsong 1981; Serpersu, Kinosita and Tsong 1985). Erythrocytes were also used to
demonstrate that DNA delivery into a cell is associated with dielectric breakdown of the
cell membrane (Auer, Brandner, and Bodemer 1976).
A large body of work has also been carried out on the interaction of small spheroidal
cells with external fields, motivated by application to cardiac defibrillation. The literature included investigation of cell excitation (Tung and Borderies 1992; Krassowska and
Neu 1994; Fishler et al. 1996; Cheng, Tung, and Sobie 1999) and membrane electroporation (O’Neill and Tung 1991; DeBruin and Krassowska 1998, 1999).
Applications of cellular electric stimulation can roughly be divided into two broad
groups. On the one hand, electric fields can be used as tools to modify various properties and responses of cells such as increases in membrane permeability for introducing
various molecules and drugs into cells (Neumann et al. 1982; Mir et al. 1995; Sersa et al.
1995; Mouneimne et al. 1990; Raffy and Teissié 1995), fusion of cells (Zimmermann
1982; Sowers 1987), physical separation of different cell types (Arnold 2001), the killing
of nonhealthy cells, and neuromuscular manipulation for therapy (Wang et al. 2002).
The other aspect of electric pulsing is geared toward its utility to characterize various
properties of biological cells or their constituents, both in suspensions and in tissues.
Among the most important approaches in such characterization is the evaluation of
cellular responses to electric fields at different frequencies. By varying the frequency
of the field, values of the measured parameters form a spectrum. Values of frequencydependent bulk dielectric permittivity of suspensions or tissues, cellular angular velocity in rotating electric fields, and the dielectrophoretic spectrum evaluation are some
of the important aspects that can be assessed (Foster and Schwan 1989; Führ, Glaser,
and Hagedorn 1985), which would otherwise be difficult to measure. The characterization techniques rely on the fact that dielectric properties of biological systems typically
display extremely high dielectric permittivity at low frequencies and fall off in distinct
steps with increasing frequency. These frequency-dependent changes permit identification and investigation of a number of completely different underlying processes.
The basic mechanism underlying a majority of these methods and field induced
biophenomena is the induction of a potential difference across the membrane by the
external electric field. The seat of the electric field–driven bioresponses tends to be
membranes because these sheaths represent nonconducting barriers that can easily be
charged by external voltage pulsing. Consequently, large electric fields can be created
across membranes that can then drive a host of bioeffects. The membranes are crucial
not only because high electric fields can be created in these regions but also because
important biological processes (e.g., irreversible apoptosis) are launched from these
sites. For example, the extrinsic apoptotic pathway (Green 2000; Peter and Krammer
2003) involves the clustering of molecules such as the tumor necrosis factor-related
apoptosis-inducing ligand (TRAIL), Fas-associated protein with death domain (FADD),
and procaspase-8 leading to the formation of the death-inducing production. This in
turn sets into motion a series of biochemical reactions that eventually lead to apoptosis
Electromagnetic Fields in Biological Systems
observable effect was the rapid increase of electrical conductivity. The conductivity
change was attributed to pore formation in the lipid bilayer membrane. Further evidence for chemical transport through membranes involved experiments with red blood
cells (Sukhorukov, Mussauer, and Zimmermann 1998; Kinosita and Tsong 1977; Teissie
and Tsong 1981; Serpersu, Kinosita and Tsong 1985). Erythrocytes were also used to
demonstrate that DNA delivery into a cell is associated with dielectric breakdown of the
cell membrane (Auer, Brandner, and Bodemer 1976).
A large body of work has also been carried out on the interaction of small spheroidal
cells with external fields, motivated by application to cardiac defibrillation. The literature included investigation of cell excitation (Tung and Borderies 1992; Krassowska and
Neu 1994; Fishler et al. 1996; Cheng, Tung, and Sobie 1999) and membrane electroporation (O’Neill and Tung 1991; DeBruin and Krassowska 1998, 1999).
Applications of cellular electric stimulation can roughly be divided into two broad
groups. On the one hand, electric fields can be used as tools to modify various properties and responses of cells such as increases in membrane permeability for introducing
various molecules and drugs into cells (Neumann et al. 1982; Mir et al. 1995; Sersa et al.
1995; Mouneimne et al. 1990; Raffy and Teissié 1995), fusion of cells (Zimmermann
1982; Sowers 1987), physical separation of different cell types (Arnold 2001), the killing
of nonhealthy cells, and neuromuscular manipulation for therapy (Wang et al. 2002).
The other aspect of electric pulsing is geared toward its utility to characterize various
properties of biological cells or their constituents, both in suspensions and in tissues.
Among the most important approaches in such characterization is the evaluation of
cellular responses to electric fields at different frequencies. By varying the frequency
of the field, values of the measured parameters form a spectrum. Values of frequencydependent bulk dielectric permittivity of suspensions or tissues, cellular angular velocity in rotating electric fields, and the dielectrophoretic spectrum evaluation are some
of the important aspects that can be assessed (Foster and Schwan 1989; Führ, Glaser,
and Hagedorn 1985), which would otherwise be difficult to measure. The characterization techniques rely on the fact that dielectric properties of biological systems typically
display extremely high dielectric permittivity at low frequencies and fall off in distinct
steps with increasing frequency. These frequency-dependent changes permit identification and investigation of a number of completely different underlying processes.
The basic mechanism underlying a majority of these methods and field induced
biophenomena is the induction of a potential difference across the membrane by the
external electric field. The seat of the electric field–driven bioresponses tends to be
membranes because these sheaths represent nonconducting barriers that can easily be
charged by external voltage pulsing. Consequently, large electric fields can be created
across membranes that can then drive a host of bioeffects. The membranes are crucial
not only because high electric fields can be created in these regions but also because
important biological processes (e.g., irreversible apoptosis) are launched from these
sites. For example, the extrinsic apoptotic pathway (Green 2000; Peter and Krammer
2003) involves the clustering of molecules such as the tumor necrosis factor-related
apoptosis-inducing ligand (TRAIL), Fas-associated protein with death domain (FADD),
and procaspase-8 leading to the formation of the death-inducing production. This in
turn sets into motion a series of biochemical reactions that eventually lead to apoptosis