Release of Proteins from Nanochannel Delivery Systems: A Coupled Many-Scale Simulation - Experimental Investigation

Transport and surface interactions of proteins in nanopore membranes play a key role in many processes of biomedical importance. Although the use of porous materials provides a large surface-to-volume ratio, the efficiency of the operations is often determined by transport behavior, and this is complicated by the fact that transport paths (i.e., the pores) are frequently of molecular dimensions. Under these conditions, wall effects become significant, with the mobility of molecules being affected by hydrodynamic interactions between protein molecules and the wall. Modeling of transport in pores is normally carried out at the continuum level, making use of such parameters as hindrance coefficients; these in turn are typically estimated using continuum methods applied at the level of individual diffusing particles. In this work we coupled experimental evidences to manyscale molecular simulations for the analysis of hen egg-white lysozyme adsorption/diffusion through a microfabricated silicon membrane, having pores of nanometric size in only one dimension. Our joint efforts allowed us a) to elucidate the specific mechanisms of interaction between the biopolymer and the silicon surface, and b) to derive molecular energetic and structural parameters to be employed in the formulation of a mathematical model of diffusion, thus filling the gap between the nano- and the macroscale.