Solid and Liquid Surface-Supported Bacterial Membrane Mimetics as a Platform for the Functional and Structural Studies of Antimicrobials

Abstract

Increasing antibiotic resistance has provoked the urgent need to investigate the interactions of antimicrobials with bacterial membranes. The reasons for emerging antibiotic resistance and innovations in novel therapeutic approaches are highly relevant to the mechanistic interactions between antibiotics and membranes. Due to the dynamic nature, complex compositions, and small sizes of native bacterial membranes, bacterial membrane mimetics have been developed to allow for the in vitro examination of structures, properties, dynamics, and interactions. In this review, three types of model membranes are discussed: monolayers, supported lipid bilayers, and supported asymmetric bilayers; this review highlights their advantages and constraints. From monolayers to asymmetric bilayers, biomimetic bacterial membranes replicate various properties of real bacterial membranes. The typical synthetic methods for fabricating each model membrane are introduced. Depending on the properties of lipids and their biological relevance, various lipid compositions have been used to mimic bacterial membranes. For example, mixtures of phosphatidylethanolamines (PE), phosphatidylglycerols (PG), and cardiolipins (CL) at various molar ratios have been used, approaching actual lipid compositions of Gram-positive bacterial membranes and inner membranes of Gram-negative bacteria. Asymmetric lipid bilayers can be fabricated on solid supports to emulate Gram-negative bacterial outer membranes. To probe the properties of the model bacterial membranes and interactions with antimicrobials, three common characterization techniques, including quartz crystal microbalance with dissipation (QCM-D), surface plasmon resonance (SPR), and neutron reflectometry (NR) are detailed in this review article. Finally, we provide examples showing that the combination of bacterial membrane models and characterization techniques is capable of providing crucial information in the design of new antimicrobials that combat bacterial resistance.

Bacterial Membrane Mimetics: From Biosensing to Disease Prevention and Treatment

“…Typical bacterial plasma membrane phospholipids include phosphatidylglycerol (PG), cardiolipin (CL), and phosphatidylethanolamine (PE) [10,11]. The composition varies greatly in different and within the same Gram-type bacterial species, where a high degree of structural, chemical, and functional variation exists in lipid membranes [16][17][18]. Therefore, many biomimetic bacterial membrane models have been developed over the last century to study their properties, structure, and physicochemical processes [19].…”

“…Numerous experiments have been conducted on model bacterial membranes utilizing this technique, most frequently using monolayers made of phospholipid mixtures such as dimyristoyl phosphatidylglycerol (DMPG), dimyristoyl phosphoethanolamine (DMPE), and CL at various ratios [68]. As model membranes for Gram-positive membranes and Gram-negative inner membranes, Langmuir monolayers composed of pure bacterial phospholipids (PE, PG, CL) or mixtures of phospholipids have been used [16]. In a study by Perczyk et al [69], models of soil bacterial membranes that varied in the mutual ratio of primary phospholipids were created utilizing single phospholipids, such as DMPE, DMPG, phosphatidylethanolamine (POPE), dipalmitoyl phosphoethanolamine (DPPE), dipalmitoyl phosphoglycerol (DPPG), and dioleoyl phosphatidylglycerol (DOPG), as well as their mixtures at different molar ratios.…”

“…Supported lipid bilayers (SLBs) are robust biomimetics that are widely used as models for mammalian and bacterial membranes [16,35]. There are different types of supported lipid membranes, such as solid-supported, tethered, or polymer-cushioned lipid bilayers.…”

“…One popular method to form SLBs is vesicle fusion due to its simplicity [16]. The formation of small vesicles is usually performed by tip sonification or extrusion through a filter [35,52,77].…”

“…As an alternative to vesicle fusion, Langmuir-Blodgett/Langmuir-Schaefer (LB/LS) deposition has been used to assemble advanced models of bacterial SLBs [16,35]. This technique deposits lipid bilayers on substrates by combining the vertical dipping Langmuir-Blodgett (LB) deposition technique with the horizontal dipping Langmuir-Schaefer (LS) technique.…”