What Is Macromolecular Crowding?

As macromolecular machines, enzymes conduct their designated work in the confined and crowded spaces inside living cells. How does a protein work in such a condition? Functions of proteins are strongly dependent on their structural stability and dynamics while the (macro) molecular interactions are arguably affected by the complexity and diversity of their environments. To date, two interrelated cellular conditions — ‘macromolecular crowding’ resulted from the effect of volume exclusion by one soluble macromolecule on another, and ‘macromolecular confinement’ originated from the effect of volume exclusion on a soluble macromolecule — have been dealt with separately. In reality, the cell membranes can form aqueous compartments as small as few tens of nanometers, containing proteins with concentration up to 40% in volume as well as imparting the dual effect of a concomitant crowding and confinement. However, such a complex architecture of cell membranes consisting of numerous components, which can modulate interaction with the encapsulated soluble proteins, is almost unmanageable to be reproduced in vitro. …show more content…
Both of these effects significantly alter the protein folding energetics, often destabilizing the protein (supra) structure. Moreover, insights into protein dynamics (crucial factors for catalytic activities) are often limited by the strong interactions between the confinement/crowding agents and the protein, causing ‘unnatural’ protein denaturation driven by the crowding agents.11 Such artificial settings do not particularly depict the usual conditions experienced within the cell interior, where hydration and protein-protein interactions play critical roles in regulating the (un) folding dynamics of an