Crowder-induced compaction of stretched DNA

The genome in cells is subject to a variety of forces. Mechanical forces arise from the fact that genomic DNA is tethered and topologically constrained by proteins while being worked on by molecular motors that pull, bend and twist it. Entropic forces arise from crowding. Indeed, cells are crowded environments with up to 40% of their volume occupied by biomolecules. Although crowding is known to compact DNA, a unified, quantitative theory that accounts for the effect of both crowding and tension is lacking. We developed a phenomenological theoretical model that does that and tested it on two sets of different measurements performed in two different laboratories using different experimental approaches to characterize the effect of polyethylene glycol (PEG) of different sizes and dextran on the DNA globule-chain transition. The model fits the data exceptionally well. It is predictive of the critical force at which a condensed DNA starts unfolding in pulling experiments, as well as of the critical crowder volume fraction at which an extended DNA molecule will start transitioning to the globular phase as tension is dropped to any given final value. Both the pulling and relaxation measurements provide the first experimental evidence for the existence of the tadpole intermediate during the phase change from chain to globule and viceversa.