Abstract
The intracellular environment represents an extremely crowded milieu, with a limited amount of free water and an almost complete lack of unoccupied space. Obviously, slightly salted aqueous solutions containing low concentrations of a biomolecule of interest are too simplistic to mimic the “real life” situation, where the biomolecule of interest scrambles and wades through the tightly packed crowd. In laboratory practice, such macromolecular crowding is typically mimicked by concentrated solutions of various polymers that serve as model “crowding agents”. Studies under these conditions revealed that macromolecular crowding might affect protein structure, folding, shape, conformational stability, binding of small molecules, enzymatic activity, protein-protein interactions, protein-nucleic acid interactions, and pathological aggregation. The goal of this review is to systematically analyze currently available experimental data on the variety of effects of macromolecular crowding on a protein molecule. The review covers more than 320 papers and therefore represents one of the most comprehensive compendia of the current knowledge in this exciting area.
Highlights
IntroductionIn solutions with increasing concentrations of such particles, the number of ways that can be used to place added molecules is progressively limited since the volume of solution available to the new molecules is progressively restricted to the part of space from which they are not excluded [15]
Slightly salted aqueous solutions containing low concentrations of a biomolecule of interest are too simplistic to mimic the “real life” situation, where the biomolecule of interest scrambles and wades through the tightly packed crowd. In laboratory practice, such macromolecular crowding is typically mimicked by concentrated solutions of various polymers that serve as model “crowding agents”
When a single-molecule method based on atomic force microscopy (AFM) was used to investigate the effects of macromolecular crowding on the forces required to unfold individual protein molecules, it was concluded that the mechanical stability of a protein can be dramatically increased by macromolecular crowding [143]
Summary
In solutions with increasing concentrations of such particles, the number of ways that can be used to place added molecules is progressively limited since the volume of solution available to the new molecules is progressively restricted to the part of space from which they are not excluded [15] The consequence of this phenomenon is decreased randomness of the particle distribution in the concentrated solutions leading to the noticeable decrease in the entropy of the crowded solution. It shows that the major mechanism by which macromolecular crowding is expected to affect proteins is related to the minimization of excluded volume. The lack of significant interaction between the protein and crowder should be demonstrated and/or experiments should be analyzed in media with different crowding agents
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