Summary: Experimental work on mixing in microfluidic devices has been of growing importance in recent years. Interest in probing reaction kinetics faster than the minute or hour time scale has intensified research in designing microchannel devices that would allow the reactants to be mixed on a time scale faster than that of the reaction. Particular attention has been paid to the design of microchannels in order to enhance the advection phenomena in these devices. Ultimately, in vitro studies of biological reactions can now be performed in conditions that reflect their native intracellular environments. A. Liau et al. [Anal. Chem. 77, 7618 (2005)] have demonstrated a droplet-based microfluidic mixer that induces improved chaotic mixing of crowded solutions in milliseconds due to protrusions (‘bumps’) on the microchannel walls. Liau et al. [loc. cit.] have shown it to be possible to mix rapidly plugs of highly concentrated protein solutions such as bovine hemoglobin and bovine serum albumin. The present work concerns an analysis of the underlying mechanisms of shear stress transfer at liquid-liquid interfaces and associated enhanced mixing arising from the protrusions along the channel walls. The role of non-Newtonian rheology and surfactants is also considered within the mixing framework developed by Aref, Ottino and Wiggins in several publications. Specifically, we show that proportional thinning of the carrier fluid lubrication layer at the bumps leads to greater advection velocities within the plugs, which enhances mixing. When the fluid within the plugs is Newtonian, mixing will be enhanced by the bumps if they are sufficiently close to one another. Changing either the rheology of the fluid within the plugs (from Newtonian to non-Newtonian) or modifying the mechanics of the carrier fluid-plug interface (by populating it with insoluble surfactants) alters the mixing enhancement.