title: Effects of crowding on the thermal stability of heterogeneous protein solutions.
abstract: 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.
authors.affiliation: Department of Surgery, MC 6035, The University of Chicago, Chicago, MC6035, Illinois 60637, USA. fdespa@uchicago.edu
authors.forename: Florin
authors.initials: F
authors.lastname: Despa
authors.forename: Dennis P
authors.initials: DP
authors.lastname: Orgill
authors.forename: Raphael C
authors.initials: RC
authors.lastname: Lee
mesh_terms: D000818:Animals; D002056:Burns / Q000378:metabolism; D006801:Humans; D008956:Models, Chemical; D011489:Protein Denaturation; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism; D012996:Solutions; D013816:Thermodynamics
chemical_list: D011506:Proteins; D012996:Solutions