Resolving the Discrepancies Between Empirical and Rayleigh Charge Limiting Models for Globular Proteins

Area of Science:

• Physical Chemistry
• Analytical Chemistry
• Biophysics

Background:

• The Rayleigh charge limiting model often shows discrepancies with experimental electrospray ionization mass spectrometry (ESI MS) data for globular proteins.
• Understanding droplet formation and charge limits in ESI MS is crucial for accurate protein analysis and characterization.

Purpose of the Study:

• To reconcile the Rayleigh model with experimental ESI MS data for globular proteins by introducing a mass-dependent density.
• To determine critical parameters like surface tension at the liquid-to-gas phase transition relevant to ESI MS.

Main Methods:

• Re-evaluation of the Rayleigh charge limiting model using published ESI MS datasets for globular proteins.
• Analysis of mass density (ρ) dependence on protein mass (M) using the relationship ρ(M)∝ M^-α.
• Establishing an equivalence between ESI MS and X-ray techniques to infer surface tension.

Main Results:

• A weak second-order dependence of mass density on mass for globular proteins was identified (α ≈ 0.14).
• A critical surface tension of 15.6 ± 5.2 mN/m was determined for droplet formation at the liquid-to-gas transition.
• The packing density factor (η) for globular proteins is estimated to be between 1 and 4.6.

Conclusions:

• The revised approach provides a more consistent picture of ESI MS phenomena for globular proteins.
• Findings are valuable for molecular dynamics simulations and understanding liquid-to-gas phase transitions.
• Results facilitate cross-calibration between ESI MS, Ion Mobility Mass Spectrometry (IM MS), Nuclear Magnetic Resonance (NMR), and X-ray crystallography.