The enzymatic hydrolysis of cellulose by cellulases is a thermodynamically challenging catalytic process that requires understanding both substrate-related and enzyme-related effects. However, the relationship between dynamic change of substrate structure and the functionality of various cellulases components during enzymatic hydrolysis has not been extensively studied, and consequently limiting research has been successful to maximize the sugar yields at very low cost. A restart method was applied to discern physical and chemical structure features of reactive intermediate and reaction products in both solid and liquid as they degrade/transform/react. The effect of enzyme-substrate interactions on reaction rates was studied using purified key cellulase components from wild type Trichoderma reesei. Synergism of these key cellulase components was studied by comparing the interrupted enzymatic hydrolysis of cellulose measured through the restart protocol with uninterrupted hydrolysis. The dynamic hydrolysis behaviors of individual key cellulase components, such as adsorption and desorption, were also monitored. Cellulose reactivity with enzymes, monomeric/oligomeric sugars, and reducing ends groups were characterized over the time course of cellulose hydrolysis. Gel permeation chromatography and nuclear magnetic resonance techniques were utilized to identify structural elements of importance, including molecular weight distribution, DP, and crystallinity index. Effects of cellulose reactivity, accessibility to cellulases and cellulase processivity on enzymatic hydrolysis of cellulose were addressed in the study. New data, models, insights, and mechanisms will be discussed in this presentation.