Evaluating the Impact of Phosphate‐Buffered Saline Solutions on the Micellar Behavior of Dimeric Surfactants and Their Interaction With Lipid Membranes

ABSTRACT Over the past few years, dicationic alkylammonium bromide dimeric surfactants have emerged as promising agents for numerous biotechnology and medical applications. However, there have been few studies examining their behavior within a biological context, particularly regarding the impact physiological buffers have on their physico‐chemical properties and how these differences impact their ability to interact with cellular lipid membranes. In this paper, we have determined the CMC values of a series of 10 and 12‐carbon main chain dimeric surfactants as a function of both spacer group length and the amount of a physiological buffer in solution, namely phosphate‐buffered‐saline (or PBS), a buffer that is relevant for biological systems under saline conditions. The impact of micellar and sub‐micellar surfactant concentrations on the phase behavior and structural integrity of model membrane systems was assessed using fluorogenic probes and correlated with cell cytotoxicity using a hemolysis assay. These results reveal a connection between the structure of the dimeric surfactants and how they interact with biological membranes. These results represent an important first step in elucidating the mechanism of the interaction of dicationic alkylammonium bromide dimeric surfactant‐mediated membrane insertion (and possible destabilization), and how this might impact the behavior of these surfactants in biochemical applications.