Effects of macromolecular crowding on the collapse of biopolymers

Experiments show that macromolecular crowding modestly reduces the size of intrinsically disordered proteins even at a volume fraction (ϕ) similar to that in the cytosol, whereas DNA undergoes a coil-to-globule transition at very small ϕ. We show using a combination of scaling arguments and simulations that the polymer size R̅(g)(ϕ) depends on x=R̅(g)(0)/D, where D is the ϕ-dependent distance between the crowders. If x≲O(1), there is only a small decrease in R̅(g)(ϕ) as ϕ increases. When x≫O(1), a cooperative coil-to-globule transition is induced. Our theory quantitatively explains a number of experiments.