Protein dielectrophoresis: Key dielectric parameters and evolving theory

Abstract

Globular proteins exhibit dielectrophoresis (DEP) responses in experiments where the applied field gradient factor ∇E2 appears far too small, according to standard DEP theory, to overcome dispersive forces associated with the thermal energy kT of disorder. To address this a DEP force equation is proposed that replaces a previous empirical relationship between the macroscopic and microscopic forms of the Clausius–Mossotti factor. This equation relates the DEP response of a protein directly to the dielectric increment δε+ and decrement δε− that characterize its β‐dispersion at radio frequencies, and also indirectly to its intrinsic dipole moment by way of providing a measure of the protein's effective volume. A parameter Γpw, taken as a measure of cross‐correlated dipole interactions between the protein and its water molecules of hydration, is included in this equation. For 9 of the 12 proteins, for which an evaluation can presently be made, Γpw has a value of ≈4600 ± 120. These conclusions follow an analysis of the failure of macroscopic dielectric mixture (effective medium) theories to predict the dielectric properties of solvated proteins. The implication of a polarizability greatly exceeding the intrinsic value for a protein might reflect the formation of relaxor ferroelectric nanodomains in its hydration shell.

Protein Dielectrophoresis: I. Status of Experiments and an Empirical Theory

“…This empirical-based suggestion mirrors various theoretical findings of Matyushov and co-workers [8,10]. The possible significance of this for further development of a robust theory for protein DEP is discussed in an accompanying paper [11].…”

“…The purpose of this and an accompanying paper [11] is to critically evaluate the protein DEP literature, to derive an empirical-based theory, and to then describe and summarize the molecular-based theory developed by Matyushov and colleagues [8,10]. In this paper we examine aspects of the reported protein DEP work not covered in previous reviews, and conclude that the reported DEP responses for a range of proteins are largely consistent.…”

“…In our opinion, the most promising theory currently being developed for protein DEP is that emerging from Matyushov's group [8,10]. An attempt to summarize this is given in the accompanying paper [11], within the frameworks of the development and application of the molecular CM-relation in classical dielectric theory; the key dielectric properties of solvated proteins; the published work on protein DEP.…”

iDEP-assisted isolation of insulin secretory vesicles

“…There is an ongoing evolution of the theoretical underpinnings of electric field gradient techniques, where past physical descriptors were limited to conductivity and permittivity of the particle. 20 It is becoming better understood that the overall structure and subtle details of the bioparticle, including the particle-solvent cross polarizations, will influence these forces [20][21][22]55,56 . This new view of the forces imparted on the insulin vesicles aligns with a rather simple proposition that the makeup of the particle has changed: something has been added, subtracted, or altered which changed the force on the particle in a measurable and quantifiable way.…”

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

“…For the Lorentz cavity field employed in the derivation of [CM] molecular , there is a maximum cavity size above which cavity field theory breaks down. This interesting situation [24] could provide an experimental approach to determining and controlling a threshold for the particle size above which protein DEP is governed by [CM] macro rather than [CM] molecular . For example, in an assessment of future protein-based drug carriers, standard DEP theory correctly predicts the reported separation by negative DEP of micron-sized designer protein particles according to their size and shape [25].…”