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Updated: Jun 10, 2026
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Microfluidic Mixers for Studying Protein Folding
Published on: April 10, 2012
Extremely slow intramolecular diffusion in unfolded protein L
Steven A Waldauer1, Olgica Bakajin, Lisa J Lapidus
1Department of Physics and Astronomy, Michigan State University, East Lansing, MI, USA.
Summary
Protein folding theories depend on diffusion rates. This study observed intramolecular diffusion in unfolded protein L, finding it significantly slower than in denaturant conditions, impacting folding rate predictions.
Area of Science:
- Protein dynamics and biophysics
- Molecular folding mechanisms
Background:
- The rate of diffusion across protein energy landscapes is key to folding theories.
- Understanding intramolecular diffusion is crucial for predicting protein folding rates.
Purpose of the Study:
- To measure the rate of intramolecular diffusion in the unfolded B1 domain of protein L.
- To investigate the relationship between diffusion rates and protein folding kinetics.
Main Methods:
- Utilized a microfluidic mixer to observe intramolecular diffusion in unfolded protein L.
- Compared diffusion rates in native conditions to those in 6 M GdnHCl (guanidinium hydrochloride).
Main Results:
- Intramolecular diffusion rates were found to be approximately 20 times slower than in 6 M GdnHCl.
- The intramolecular diffusion coefficient decreased 100-500 times due to increased compactness.
- This diffusion slowdown occurred rapidly within the 250-microsecond mixing time.
Conclusions:
- Observed folding rates are accurately predicted by a Kramers model incorporating a denaturant-dependent diffusion coefficient.
- The diffusion coefficient appears to be a significant factor contributing to the observed protein folding rates.
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