Kinetic hysteresis in collagen folding

Area of Science:

• Biophysics
• Materials Science
• Structural Biology

Background:

• Collagen's triple helix exhibits distinct thermal unfolding and refolding behaviors, characterized by hysteresis.
• Hysteresis loop shape is influenced by temperature change rates and peptide concentration.
• Experimental conditions often exceed natural unfolding and refolding rates.

Purpose of the Study:

• To quantitatively investigate the hysteresis phenomenon in collagen model peptides.
• To elucidate the kinetic mechanisms governing collagen triple helix formation and stability.
• To determine conditions for measuring true equilibrium transitions.

Main Methods:

• Differential scanning calorimetry (DSC) on collagen model peptides at varying heating/cooling rates and concentrations.
• Kinetic modeling to fit unfolding and refolding data, considering nucleation and propagation steps.
• Analysis of exogenously trimerized collagen models using simplified kinetic mechanisms.

Main Results:

• A single kinetic model quantitatively described both forward (unfolding) and backward (refolding) reactions.
• True equilibrium transitions require slow scanning rates and high peptide concentrations.
• (Gly-Pro-4(R)Hyp)(10) peptides exhibit significantly faster folding than (Gly-Pro-Pro)(10) due to a more stable nucleus.

Conclusions:

• The study provides a quantitative framework for understanding collagen hysteresis based on kinetic mechanisms.
• Folding rates are primarily determined by nucleus stability, while propagation rates are similar.
• The presented analysis is applicable to deriving kinetic and thermodynamic data for collagenous and other systems exhibiting kinetically controlled hysteresis.