In this Omecamtiv mecarbil investigation, a detailed methodology to study surface interactions between aquatic NOM and membranes is described. Gartempe River NOM and Brittany River NOM, both rigorously characterized in previous studies, were selected as model humic and biopolymer aquatic NOM isolates, respectively. Two manufactured membranes (PA and PS) were selected due to their different properties. AFM was used as a sensitive technique that allows the study of specific and non-specific interactions at the interface . Moreover, AFM can be adapted to closely mimic engineered water systems or aquatic environments by the measurement of interacting forces in solution of varied but controlled chemistry. The dominant mechanisms that govern NOM–membrane interactions as a function of their physicochemical characteristics and solution chemistry were proposed and correlated to the results of previous studies. The merit of this research is to advance our fundamental understanding of conditioning film formation during NOM-fouling, which would aid in the design and optimization of membrane coatings.