Do the concepts of Newtonian and non-Newtonian fluids still hold at a nanoscopic level? Recently I've spent a great deal of time thinking about enzyme diffusion in cytoplasm. One thing that keeps me awake at night is the constant referral to cytoplasm as a non-Newtonian fluid (which it surely is when looking at it as a whole), and the implications this has for the diffusive properties of singular enzymes.

If I think about a single enzyme in the cytoplasm with its immediate surroundings, I would expect to find the protein with its solvation shells, and only a few non-water components. In this context I'm unable to understand how this single enzyme could be thought to be in a non-Newtonian medium.

Furthermore, when thinking about the diffusion of the enzyme, quite a few authors refer to the Scallop theorem, and define it in the context of non-Newtonian fluids. If the enzyme is mostly surrounded by water molecules, and only occasionally runs in to other proteins or peptides, shouldn't the protein be considered to reside in a Newtonian medium?

Shortly put: How far down can you go until the classification between Newtonian and non-Newtonian fluids starts to break down?
Generally Fick's laws of diffusion have been found to apply pretty well to molecular translational and rotational diffusion in solution. This means that we assume that the solvent is a continuous structureless fluid, which in practice means that the diffusing molecule should be far bigger than that of the solvent so that the solvent's molecular nature can be ignored. Surprisingly this works well with 'slip' and 'stick' boundary conditions down to situations where the solute is not that much bigger than the solvent, e.g.  rhodamine and similar dye molecules in solvents such as acetonitrile or ethanol. In your example of a protein in water then you might expect that it would behave 'normally' as just described.

However, in the cytoplasm the close packing of many similar sized and large molecules means that these can easily block the diffusion of any other (except for far, far smaller ones such as water) and so the situation is totally different and will be more like a percolation process where a slight reduction in packing can lead to a large, almost stepwise increase in diffusion coefficient. The idea of a single diffusion coefficient is therefore not helpful.