Crowding can substantially affect the transition of a protein between its native (N) and unfolded (U) states via volume exclusion effects. Also, it influences considerably the aggregation (A) of unfolded proteins. To examine the details, we developed an approach for computing the kinetic rates of the process N ↔ U → A in which the concentration of the protein is explicitly taken into account. We then compute the relative change with temperature of the protein denaturation for various fractional volume occupancies and partition of proteins in solution. The analysis indicates that, in protein solutions in which the average distance between proteins is comparable with the radius of gyration of an unfolded protein, steric effects increase the stability of the proteins which are in compact, native states. In heterogeneous protein solutions containing various types of proteins with different thermal stabilities, the unfolding of the most thermolabile proteins will increase the stability of the other proteins. The results shed light on the way proteins change the thermal stability of a cell as they unfold and aggregate. This study may be valuable in questions related to the dynamics of thermal injuries.
|Number of pages||7|
|Journal||Annals of Biomedical Engineering|
|State||Published - Nov 2005|
Bibliographical noteFunding Information:
The research presented here has been partly supported by the National Institutes of Health, grants R01 GM61101 (RCL) and R01 GM64757 (RCL), and The Electric Power Research Institute (RCL).
- Crowding effects
- Lumry-Eyring model
- Protein denaturation
- Thermal injury
ASJC Scopus subject areas
- Biomedical Engineering