Thermal properties of human IgG

Area of Science:

• Biophysics
• Materials Science
• Chemical Kinetics

Background:

• Human immunoglobulin G (IgG) is a crucial protein with applications in therapeutics and diagnostics.
• Understanding IgG aggregation is vital for predicting its stability and efficacy.
• Heat-induced aggregation is a common challenge in protein formulation and storage.

Purpose of the Study:

• To investigate the kinetics of heat-induced aggregation of human IgG.
• To characterize the aggregation process using dynamic light scattering.
• To determine the scaling laws and thermodynamic parameters governing IgG aggregation.

Main Methods:

• Dynamic light scattering (DLS) was employed to monitor IgG solutions heated above 50°C.
• Scattering intensity and effective hydrodynamic radius were measured over time.
• Data were analyzed using the Smoluchowski aggregation model and power-law scaling.

Main Results:

• IgG aggregation and irreversible cluster growth were observed above 50°C.
• The aggregation process followed Smoluchowski kinetics with characteristic power-law behavior for radius and intensity.
• A fraction of IgG monomers (approx. 0.48) showed heat stability up to 63°C.
• Scaling exponents alpha_R = 0.48, alpha_I = 1.00, and beta = 0.39 were determined.
• The aggregation was identified as an activated process with Gibbs free energy (ΔG*) of 13.8 kcal/mole and enthalpy of activation (ΔH*) of 120 kcal/mole.

Conclusions:

• The study successfully characterized IgG heat aggregation kinetics using DLS and Smoluchowski modeling.
• Power-law scaling and data collapse confirm the universality of the observed aggregation process.
• The determined thermodynamic parameters provide insights into the activation energy and stability of IgG during heating.