Are nucleation kinetics of protein crystals similar to those of liquid droplets?

We have studied the nucleation of crystals of a model protein from aqueous solutions using a never technique that allows direct determinations of homo geneous nucleation rates. At a constant temperature of 12.6 degrees C we va ried the thermodynamic supersaturation by changing the concentrations of pr otein and precipitant. We found a broken dependence of the homogeneous nucl eation rate on supersaturation that is beyond the predictions of the classi cal nucleation theory. The nucleation theorem allows us to relate this to d iscrete changes of the size of the crystal nuclei with increasing supersatu ration as (10 or 11) -> (4 or 5) -> (1 or 2). Furthermore, we observe that the existence of a second liquid phase at high protein concentrations stron gly affects crystal nucleation kinetics: (i) Crystal nucleation rates are l ower than expected in the phase region of liquid-liquid demixing. (ii) In t he immediate proximity of this region, nucleation rates vary by factors of up to 2 in identical experiments. Since for this region theory predicts a s harp rate maximum, we attribute this kinetic instability to minor shifts of the experimental conditions toward or away from the phase boundary.