Fig. 1

Three familiar models of macromolecular transport under confinement, and the topologically frustrated dynamical state. a Ogston’s model, b Reptation, and c Entropic Barrier. d Cartoon of topological frustration when large guest macromolecules are crowded in a gel matrix. In c, where R _g of the guest molecule is comparable to the mesh size ξ of the gel, the molecule diffuses by negotiating essentially single entropic barriers. In d, R _g is much bigger than the mesh size ξ which itself is sufficiently big to hold large numbers of fluctuating monomers. Each macromolecule occupies tens of meshes with a family of local relaxation rates, and redistribution of portions of the molecule involves multiple entropic barriers which are strongly correlated. All of these barriers must be simultaneously breached by the guest molecule for it to move a distance comparable to its size. The required enormous time for this correlated process results in the non-diffusive topologically frustrated dynamics