Up to now, experimental limitations have prevented researchers from achieving the molecular-level understanding for the initial steps of the enzymatic hydrolysis of cellulose, where cellulase breaks down the crystal structure on the surface region of cellulose and exposes cellulose chains for the subsequent hydrolysis by cellulase. Because one of these non-hydrolytic enzymatic steps could be the rate-limiting step for the entire enzymatic hydrolysis of crystalline cellulose by cellulase, being able to analyze and understand these steps is instrumental in uncovering novel leads for improving the efficiency of cellulase. In this communication, we report an innovative application of the microcantilever technique for a real-time assessment of the morphological change of cellulose induced by a treatment of sodium chloride. This sensitive nanomechanical approach to define changes in surface structure of cellulose has the potential to permit a real-time assessment of the effect of the non-hydrolytic activities of cellulase on cellulose and thereby to provide a comprehensive understanding of the initial steps of the enzymatic hydrolysis of cellulose. Biotechnol. Bioeng. 2010; 107: 190-194. (C) 2010 Wiley Periodicals, Inc.