Effects of molecular crowding and confinement on the spatial organization of a biopolymer.

A chain molecule can be entropically collapsed in a crowded medium in a free or confined space. Here, we present a unified view of how molecular crowding collapses a flexible polymer in three distinct spaces: free, cylindrical, and (two-dimensional) slit-like. Despite their seeming disparities, a few general features characterize all these cases, even though the ϕ-dependence of chain compaction differs between the two cases: a > a and a < a, where ϕ is the volume fraction of crowders, a is the monomer size, and a is the crowder size. For a > a (applicable to a coarse-grained model of bacterial chromosomes), chain size depends on the ratio aϕ/a, and "full" compaction occurs universally at aϕ/a ≈ 1; for a > a (relevant for protein folding), it is controlled by ϕ alone and crowding has a modest effect on chain size in a cellular environment (ϕ ≈ 0.3). Also for a typical parameter range of biological relevance, molecular crowding can be viewed as effectively reducing the solvent quality, independent of confinement.