Protein Dielectrophoresis: A Tale of Two Clausius-Mossottis—Or Something Else?

Abstract

Standard DEP theory, based on the Clausius–Mossotti (CM) factor derived from solving the boundary-value problem of macroscopic electrostatics, fails to describe the dielectrophoresis (DEP) data obtained for 22 different globular proteins over the past three decades. The calculated DEP force appears far too small to overcome the dispersive forces associated with Brownian motion. An empirical theory, employing the equivalent of a molecular version of the macroscopic CM-factor, predicts a protein’s DEP response from the magnitude of the dielectric β-dispersion produced by its relaxing permanent dipole moment. A new theory, supported by molecular dynamics simulations, replaces the macroscopic boundary-value problem with calculation of the cross-correlation between the protein and water dipoles of its hydration shell. The empirical and formal theory predicts a positive DEP response for protein molecules up to MHz frequencies, a result consistently reported by electrode-based (eDEP) experiments. However, insulator-based (iDEP) experiments have reported negative DEP responses. This could result from crystallization or aggregation of the proteins (for which standard DEP theory predicts negative DEP) or the dominating influences of electrothermal and other electrokinetic (some non-linear) forces now being considered in iDEP theory.