Optimizing end-labeled free-solution electrophoresis by increasing the hydrodynamic friction of the drag-tag

We study the electrophoretic separation of polyelectrolytes of varying lengths by means of endlabeled free-solution electrophoresis (ELFSE). A coarse-grained molecular dynamics simulation model, using full electrostatic interactions and a mesoscopic Lattice Boltzmann fluid to account for hydrodynamic interactions, is used to characterize the drag coefficients of different label types: linear and branched polymeric labels, as well as transiently bound micelles. It is specifically shown that the label’s drag coefficient is determined by its hydrodynamic †Frankfurt Institute for Advanced Studies, Goethe University, Ruth-Moufang-Strasse 1, D-60438 Frankfurt am Main, Germany ‡Institute for Computational Physics, University of Stuttgart, Pfaffenwaldring 27, D-70569 Stuttgart, Germany ¶Department of Physics, University of Ottawa, 150 Louis-Pasteur, Ottawa, Ontario K1N 6N5, Canada 1 ar X iv :0 90 2. 18 89 v1 [ co nd -m at .s of t] 1 1 Fe b 20 09 Kai Grass et al. Optimizing ELFSE size, and that the drag per label monomer is largest for linear labels. However, the addition of side chains to a linear label offers the possibility to increase the hydrodynamic size, and therefore the label efficiency, without having to increase the linear length of the label, thereby simplifying synthesis. The third class of labels investigated, transiently bound micelles, seems very promising for the usage in ELFSE, as they provide a significant higher hydrodynamic drag than the other label types. The results are compared to theoretical predictions, and we investigate how the efficiency of the ELFSE method can be improved by using smartly designed drag-tags. Introduction As known from experiments and theory,1–6 the free-solution mobility of a flexible polyelectrolyte chain does not depend on the chain length N (number of monomers) anymore if the chain is longer than a certain length NFD. The regime where N > NFD is called free-draining regime. In this regime, the counterions influence the inter-monomer hydrodynamic interactions and allow the fluid to drain through the polyelectrolyte coil. The effective friction Γeff becomes linear in the chain length, as does the effective charge Qeff for longer chains, which leads to a constant, length-independent mobility μ0 = Qeff Γeff . (1) It was shown that attaching a suitable uncharged molecule to an electrophoresis target can restore the size-dependent mobility and overcome the free-draining property of long polyelectrolyte chains.7–9 This method, which is known as end-labeled free-solution electrophoresis (ELFSE), is based on the alteration of the charge-to-friction ratio of the polyelectrolyte molecules by an uncharged drag label. The effect of the label can be compared to that of a parachute attached to a moving object. The additional friction provided by the parachute slows the object down. This effect is stronger for smaller molecules with a lower effective friction and smaller charge to pull the drag-tag, as the