Characterizing the Membrane-Disruptive Behavior of Dodecylglycerol Using Supported Lipid Bilayers

Abstract

Monoglycerides are esterified adducts of fatty acid and glycerol molecules that disrupt phospholipid membranes, leading to a wide range of biological functions such as antimicrobial activity. Among monoglycerides, glycerol monolaurate (GML) exhibits particularly high antimicrobial activity, although enzymatic hydrolysis of its ester group can diminish potency. Consequently, there have been efforts to identify more chemically stable versions of GML, most notably its alkylglycerol ether equivalent called dodecylglycerol (DDG). However, despite high structural similarity, biological studies indicate that DDG and GML are not functionally equivalent and it has been speculated that the two compounds might have different interaction profiles with phospholipid membranes. To address this outstanding question, herein, we employed supported lipid bilayer (SLB) platforms to experimentally characterize the interactions of DDG with phospholipid membranes. Quartz crystal microbalance-dissipation experiments identified that DDG causes concentration-dependent membrane morphological changes in SLBs and the overall extent of membrane remodeling events was greater than that caused by GML. In addition, time-lapsed fluorescence microscopy imaging experiments revealed that DDG causes extensive membrane tubulation that is distinct from how GML induces membrane budding. We discuss how differences in the head group properties of DDG and GML contribute to distinct membrane interaction profiles, offering insight into how the molecular design of DDG not only improves chemical stability but also enhances membrane-disruptive activity.

Bacterial Quorum Sensing Signals Promote Large-Scale Remodeling of Lipid Membranes

“…The changes in the bilayer structure and associated dynamics described above and shown in Figure are similar to the restructuring of SLBs reported in past studies when SLBs were placed in contact with certain natural and synthetic surfactants. ,,− In those studies, the presence of long, thin structures and pseudo-circular structures were interpreted to result from the formation of hollow microtubules and thin, water-filled, and hemispherical caps. Cartoon representations (both top-down and side view) of these structures are shown in Figure .…”

“…aeruginosa. We selected SLBs as a model system for these initial studies rather than other lipid membrane systems (such as giant unilamellar vesicles or GUVs) because they are compatible with a wide range of surface characterization techniques, including acoustic sensors (QCM-D) and fluorescence microscopy, , and can be prepared using a variety of methods. ,, DOPC was chosen as a model lipid because it is widely used as a simple laboratory model for mammalian membranes, it is fluid at room temperature, and it has been previously used by other groups to characterize the interactions of analytes with lipid membranes, thereby facilitating comparisons between the results of those past studies and the new experiments with the amphiphiles reported here. ,− To facilitate visualization by optical microscopy, the lipid membranes were doped with a 0.1 wt % fluorescently labeled lipid Rho-DPPE. In all of the fluorescence microscopy experiments described here, SLBs were formed on NaOH-treated glass in an Ibidi flow cell using the vesicle fusion (VF) technique, unless otherwise noted (see Methods for additional details) .…”

Medium-chain fatty acids and monoglycerides as feed additives for pig production: towards gut health improvement and feed pathogen mitigation

“…MCFAs and monoglycerides have unique mechanisms of disrupting phospholipid membranes and are principally active in the micellar state [31][32][33]. Monoglycerides form micelles at lower concentrations than MCFAs, which helps to explain why monoglycerides are often more biologically potent than fatty acids and longer compounds also tend to exhibit more potent inhibitory The smell level is ranked in the order of strong, moderate, mild, and minor.…”

Lipid Nanoparticle Technology for Delivering Biologically Active Fatty Acids and Monoglycerides

“…The potency of fatty acids can be tuned by the solution pH because this condition affects their charge state and hence CMC values, while monoglycerides are nonionic and exhibit consistent CMC values and stable membrane-interaction behaviors across standard pH conditions [103]. Ether-linked analogues of monoglycerides, which also have pH-stable molecular properties, have also demonstrated promising membrane-disruptive activities in related studies [104,105].…”