Conductance characteristics of nanofluidic channels (nanochannels) fall into two regimes: at low ionic concentrations, conductance is governed by surface charge while at high ionic concentrations it is determined by nanochannel geometry and bulk ionic concentration. We used aminosilane chemistry and streptavidin-biotin binding to study the effects of surface reactions on nanochannel conductance at different ionic concentrations. Immobilization of small molecules such as aminosilane or biotin mainly changes surface charge, affecting conductance only in the low concentration regime. However, streptavidin not only modifies surface charge but also occludes part of the channel, resulting in observable conductance changes in both regimes. Our observations reflect the interplay between the competing effects of charge and size of streptavidin on nanochannel conductance.