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Molecular Shielding of Electric Field Complex Dissociation

Department of Physiology, Michigan State University, East Lansing, Michigan 48824

Correspondence: Address reprint requests to Patrick F. Dillon, Tel.: 517-355-6475, ext. 1102; Fax: 517-355-5125; E-mail: dillon{at}msu.edu.

We have previously demonstrated the ability of electric fields to dissociate ascorbate and catecholamines and shown that the electric field generated by cell membranes is sufficient to produce dissociation of these complexes up to 8 nm from the cell membrane. We show here that this process is applicable to a wide range of biological complexes including small molecules (norepinephrine-morphine sulfate), protein-protein complexes (insulin-glucagon), and small molecule-protein complexes (epinephrine-bovine serum albumin). The extrapolation of the slope of the electric field dependence to zero electric field can be used to estimate the log of the dissociation constant (K_D) of a complex and, by multiplying the log(K_D) by –2.303RT, the association energy (E) of the complex. The slope of the electric field dependence is inversely related to the molecular radii, with the best fit of the slope related to E*(1/r₁ + 1/r₂), where r is the estimated radius of each molecule in the complementary pair. This indicates that the binding site of the pair is shielded by the remaining parts of the molecules, and the larger the molecule the greater the shielding. When the slope of the electric field dependence goes to 0 as r goes to infinity and 1/r goes to 0, the molecular shielding constant is 7.04 x 10^–8 cm²/V. Very large complexes will be minimally affected by the electric field due to molecular shielding and reduced electric field as their radius restricts approach to the membrane. Large protein receptors will deflect the membrane electric field and allow agonist binding.