Unraveling Membrane-Disruptive Properties of Sodium Lauroyl Lactylate and Its Hydrolytic Products: A QCM-D and EIS Study

Abstract

Membrane-disrupting lactylates are an important class of surfactant molecules that are esterified adducts of fatty acid and lactic acid and possess industrially attractive properties, such as high antimicrobial potency and hydrophilicity. Compared with antimicrobial lipids such as free fatty acids and monoglycerides, the membrane-disruptive properties of lactylates have been scarcely investigated from a biophysical perspective, and addressing this gap is important to build a molecular-level understanding of how lactylates work. Herein, using the quartz crystal microbalance–dissipation (QCM-D) and electrochemical impedance spectroscopy (EIS) techniques, we investigated the real-time, membrane-disruptive interactions between sodium lauroyl lactylate (SLL)—a promising lactylate with a 12-carbon-long, saturated hydrocarbon chain—and supported lipid bilayer (SLB) and tethered bilayer lipid membrane (tBLM) platforms. For comparison, hydrolytic products of SLL that may be generated in biological environments, i.e., lauric acid (LA) and lactic acid (LacA), were also tested individually and as a mixture, along with a structurally related surfactant (sodium dodecyl sulfate, SDS). While SLL, LA, and SDS all had equivalent chain properties and critical micelle concentration (CMC) values, our findings reveal that SLL exhibits distinct membrane-disruptive properties that lie in between the rapid, complete solubilizing activity of SDS and the more modest disruptive properties of LA. Interestingly, the hydrolytic products of SLL, i.e., the LA + LacA mixture, induced a greater degree of transient, reversible membrane morphological changes but ultimately less permanent membrane disruption than SLL. These molecular-level insights support that careful tuning of antimicrobial lipid headgroup properties can modulate the spectrum of membrane-disruptive interactions, offering a pathway to design surfactants with tailored biodegradation profiles and reinforcing that SLL has attractive biophysical merits as a membrane-disrupting antimicrobial drug candidate.

Unraveling the Biophysical Mechanisms of How Antiviral Detergents Disrupt Supported Lipid Membranes: Toward Replacing Triton X-100

“…Changes in conductance ( G m ), directly proportional to the tendency of ions to flow through the bilayer interface, and capacitance ( C m ), inversely related to membrane thickness, were measured as detergent compounds at 2 × CMC were added to the membrane, followed by a buffer rinsing step. To confirm DOPC tBLM formation, G m and C m signals in the range of < ∼3 μS and 0.7–1.2 μF/cm 2 , respectively, were deemed to be suitable, and the fabricated tBLM values served as the measurement baseline signals. Treatment involved subsequent incubation with the appropriate detergent concentration for 30 min, followed by buffer washing.…”

Membrane-Disruptive Effects of Fatty Acid and Monoglyceride Mitigants on E. coli Bacteria-Derived Tethered Lipid Bilayers

“…Herein, we conducted EIS measurements to comparatively evaluate the membrane-disruptive effects of medium-chain fatty acid and monoglyceride mitigants on E. coli tBLM platforms. Our approach builds on recent efforts to study antimicrobial lipid and detergent interactions with simplified tBLM platforms [ 28 , 29 , 30 ] and extends the measurement concept to investigate how various biologically important antimicrobial mitigants interact with reconstituted E. coli lipid membranes. As depicted in Figure 1 A, we selected two pairs of medium-chain fatty acids and monoglycerides—the 10-carbon long capric acid (CA) fatty acid and its monoglyceride equivalent monocaprin (MC), and the 12-carbon long lauric acid (LA) fatty acid and its monoglyceride equivalent glycerol monolaurate (GML)—for EIS testing because these mitigants are among the most potent, membrane-disruptive ones against Gram-positive bacteria [ 31 ], yet have varying levels of antibacterial activity against Gram-negative bacteria such as E. coli .…”