Surfactants, being the major component of soap are the most widely used disinfectants. Efforts to develop novel surfactant molecules in view of the threat of antimicrobial resistance has been challenging, due to a lack of understanding of their interactions with the bacterial cell envelope. The outer membrane in Gram negative bacteria is a complex multilayered structure posing a large barrier for the translocation of antimicrobial molecules to their sites of action across the membrane. In this study, we investigate the interactions of surfactants with the bacterial outer membrane of E. coli composed of various lipids and proteins, using molecular dynamics simulations. The behavior of surfactants was studied in their micellar as well as free states to examine the effect of aggregation. Surfactant micelles are observed to preferentially bind to the transmembrane porin OmpF as they approach the outer membrane. While bound to the extracellular loops of the OmpF, micelles are observed to hinder ionic and water transport through the channel protein. While these bulkier micelles appear to block the vestibule of outer membrane porins, it is known previously that free surfactants translocate through them. Hence, we further studied the mechanism of translocation of free surfactants through the channel porin OmpF by computing the energetics associated with the process. Free energy calculations were performed using replica exchange umbrella sampling for surfactants with varying structural properties like chain length and functional groups, to identify features that significantly modulate translocation. A significant correlation is observed between the hydrophobic chain length of surfactants and the computed free energy barrier through the porin which implicates their hydrophilic and size specificity for substrates. The study thus provides insights into previously unknown complex interactions between surfactants and the bacterial outer membrane porins depending on their structural properties and aggregation states. These observations are expected to aid in the design of novel surfactants with improved antimicrobial properties.
