Solvent‐mediated forces in protein dielectrophoresis

Abstract

DEP is an established method to manipulate micrometer‐sized particles, but standard continuum theories predict only negligible effects for nanometer‐sized proteins despite contrary experimental evidence. A theoretical description of protein DEP needs to consider details on the molecular scale. Previous work toward this goal addressed the role of orientational polarization of static protein dipole moments for dielectrophoretic effects, which successfully predicts the general magnitude of dielectrophoretic forces on proteins but does not readily explain negative DEP forces observed for proteins in some experiments. However, contributions to the protein chemical potential due to protein–water interactions have not yet been considered in this context. Here, we utilize atomistic molecular dynamics simulations to evaluate polarization‐induced changes in the protein solvation free energy, which result in a solvent‐mediated contribution to dielectrophoretic forces. We quantify solvent‐mediated dielectrophoretic forces for two proteins and a small peptide in water, which follow expectations for protein–water dipole–dipole interactions. The magnitude of solvent‐mediated dielectrophoretic forces exceeds predictions of nonmolecular continuum theories, but plays a minor role for the total dielectrophoretic force for the simulated proteins due to dominant contributions from the orientational polarization of their static protein dipoles. However, we extrapolate that solvent‐mediated contributions to negative protein DEP forces will become increasingly relevant for multidomain proteins, complexes and aggregates with large protein–water interfaces, as well as for high electric field frequencies, which provides a potential mechanism for corresponding experimental observations of negative protein DEP.

Orders-of-Magnitude Larger Force Demonstrated for Dielectrophoresis of Proteins Enabling High-Resolution Separations Based on New Mechanisms

“…Beyond the long-standing descriptions based on the CM f , through separate studies of Matyushov, , Pethig, and Heyden and Waskasi, there are a number of constructs that support a much larger force by considering interfacial polarization, detailed molecular properties of the bioparticles, and local hydrating water molecules. These evolving theories more closely reflect dielectric spectroscopic data from proteins and will undoubtedly have a large impact on understanding other forms of electric field gradient-induced actions.…”

Dielectrophoresis from the System’s Point of View: A Tale of Inhomogeneous Object Polarization, Mirror Charges, High Repelling and Snap-to-Surface Forces and Complex Trajectories Featuring Bifurcation Points and Watersheds

“…We believe that our model can explain experimental findings such as the paradoxical accumulation of viruses and proteins in field cages or at electrode edges, where the dipole approach cannot account for sufficiently high trapping forces to withstand Brownian motion [ 16 , 17 , 42 , 43 , 44 ]. Forces large enough to trap small objects can result from inhomogeneous object polarization at electrodes or other surfaces and near to other objects.…”

“…In the dipole region, the DEP forces only reach moderate magnitudes compared to the forces in front of the pointed electrode, where they reach magnitudes up to thousands of times higher than in the dipole region. Figure 8 considers the "dipole range" where the forces of the classical dipole model can be quantified and directly compared with the normalized DEP forces from Equation (16).…”

“…However, in microchambers, complicated field distribution and inhomogeneous object polarization is typical, because the objects are relatively large with respect to the chamber [ 10 , 11 , 12 , 13 , 14 , 15 ]. The simple CMF description becomes problematic because the total force results from the superposition of polarization contributions from the entire volume of the inhomogeneously polarized object with the inhomogeneous field [ 16 , 17 ]. Examples include individual objects inducing mirror charges at the electrode surface or the attraction of two adjacent objects of the same size, where each object is subject to the field resulting from the inhomogeneous polarization of the respective other object.…”

The System’s Point of View applied to Dielectrophoresis in Plate Capacitor and Pointed-versus-Pointed Electrode Chambers

“…of our new DEP model that simplifies the computation of the DEP behavior in complex field environments, something which is especially important in microchambers, where complicated field distribution and inhomogeneous object polarization are typical, because the objects are relatively large for the chamber [11][12][13][14][15][16]. The simple CMF (induced dipole) description becomes problematic [5,6,17,18] because the total force results from the superposition of contributions from the entire volume of the inhomogeneously polarized object with the inhomogeneous field.…”