Protein Dielectrophoresis in Solution.

Area of Science:

• Biophysics
• Physical Chemistry
• Computational Biology

Background:

• Dielectrophoresis (DEP) describes protein forces in electric fields, traditionally relying on a dielectric constant for susceptibility calculations.
• The Clausius-Mossotti factor, used in dielectric theories, is inadequate for describing the dipolar response of proteins and hydration water due to ill-defined dielectric constants for molecular-sized particles.

Purpose of the Study:

• To develop an alternative theory for DEP susceptibility based on molecular properties of proteins and water.
• To investigate the influence of protein tumbling on DEP susceptibility using molecular dynamics simulations.
• To establish a general relation connecting DEP susceptibility to the dielectric increment of protein solutions.

Main Methods:

• Developed a new theory for DEP susceptibility incorporating protein molecular dipole moment variance and refractive index.
• Performed molecular dynamics (MD) simulations of cytochrome c in solution to calculate dipolar susceptibilities.
• Compared MD-derived DEP susceptibility with predictions from the Clausius-Mossotti factor and experimental data (Oncley's equation).

Main Results:

• Protein tumbling on the nanosecond timescale leads to positive DEP (pulling force).
• MD simulations yielded DEP susceptibility for cytochrome c that is 10^3-10^4 times higher than predicted by the Clausius-Mossotti factor.
• The high DEP susceptibility values are consistent with Oncley's equation and experimental dielectric data for protein solutions.

Conclusions:

• The molecular dynamics-based theory provides a more accurate description of protein dielectrophoresis than traditional dielectric theories.
• Protein tumbling is a crucial factor significantly enhancing DEP susceptibility.
• A general relationship was established between DEP susceptibility and solution dielectric increment, validated by cytochrome c data.