The bacterial cell envelope is a complex multilayered structure evolved to protect bacteria in hostile environments. An understanding of the molecular basis for the interaction and transport of antibacterial therapeutics with the bacterial cell envelope will enable the development of drug molecules to combat bacterial infections and suppress the emergence of drug-resistant strains. Here we report the successful creation of an in vitro supported lipid bilayer (SLB) platform of the outer membrane (OM) of E. coli, an archetypical Gram-negative bacterium, containing the full smooth lipopolysaccharide (S-LPS) architecture of the membrane. Using this platform, we performed fluorescence correlation spectroscopy (FCS) in combination with molecular dynamics (MD) simulations to measure lipid diffusivities and provide molecular insights into the transport of natural antimicrobial agent thymol. Lipid diffusivities measured on symmetric supported lipid bilayers made up of inner membrane lipids show a distinct increase in the presence of thymol as also corroborated by MD simulations. However, lipid diffusivities in the asymmetric OM consisting of only S-LPS are invariant upon exposure to thymol. Increasing the phospholipid content in the LPS-containing outer leaflet improved the penetration toward thymol as reflected in slightly higher relative diffusivity changes in the inner leaflet when compared with the outer leaflet. Free-energy computations reveal the presence of a barrier (∼6 kT) only in the core-saccharide region of the OM for the translocation of thymol while the external Oantigen part is easily traversed. In contrast, thymol spontaneously inserts into the inner membrane. In addition to providing leafletresolved penetration barriers in bacterial membranes, we also assess the ability of small molecules to penetrate various membrane components. With rising bacterial resistance, our study opens up the possibility of screening potential antimicrobial drug candidates using these realistic model platforms for Gram-negative bacteria.

We describe measurements of the permittivity and Frank elastic constant in the nematic phase of a binary system displaying a transition between the nematic (N) and the recently discovered twist-bend nematic (NTB) phase. Among the salient features observed are (i) the existence of the NTB phase even when the system is loaded with a high concentration (∼64 mol %) of a rodlike component; (ii) a clear signature in permittivity of the N-NTB transition; and (iii) a lower value of the bend elastic constant compared to the splay over a large phase space, with the difference between the two becoming a maximum for an intermediate mixture. These studies further support the surprising idea that the elastic features associated with bent molecules can be further augmented by suitable rodlike additives.

A polymer stabilized liquid crystal (PSLC) system formed by a nematic contained in a biopolymer network of cellulose nanocrystals, exhibiting many attractive features, is demonstrated. The threshold or the minimum voltage needed to operate the electro-optic device does not depend on the concentration of the polymer, a feature that is in contrast to the standard PSLC systems. A second point, more important from the driving circuit point of view, is that the voltage-off response time drastically reduces and even becomes practically invariant over the thermal range of the nematic phase. A smart window fabricated using this biopolymer network system exhibits good contrast between the scattering and transparent states driven by voltage and shows an exceptionally high haze factor. A highlight of the device fabrication is that the employed protocol is facile, making it appealing for a potentially viable smart window application.

Surfactants with their intrinsic ability to solubilize lipid membranes are widely used as antibacterial agents, and their interactions with the bacterial cell envelope are complicated by their differential aggregation tendencies. We present a combined experimental and molecular dynamics investigation to unravel the molecular basis for the superior antimicrobial activity and faster kill kinetics of shorter-chain fatty acid surfactant, laurate, when compared with the longer-chain surfactants studied in contact time assays with live Escherichia coli (E. coli). From all-atom molecular dynamics simulations, translocation events across peptidoglycan were the highest for laurate followed by sodium dodecyl sulfate, myristate, palmitate, oleate, and stearate. The translocation kinetics were positively correlated with the critical micellar concentration, which determined the free monomer surfactant concentration available for translocation across peptidoglycan. Interestingly, aggregates showed a lower propensity to translocate across the peptidoglycan layer and longer translocation times were observed for oleate, thereby revealing an intrinsic sieving property of the bacterial cell wall. Molecular dynamics simulations with surfactant-incorporated bacterial inner membranes revealed the greatest hydrophobic mismatch and membrane thinning in the presence of laurate when compared with the other surfactants. The enhanced antimicrobial efficacy of laurate over oleate was further verified by experiments with giant unilamellar vesicles, and electroporation molecular dynamics simulations revealed greater inner membrane poration tendency in the presence of laurate when compared with the longer-chain surfactants. Our study provides molecular insights into surfactant translocation across peptidoglycan and chain length-induced structural disruption of the inner membrane, which correlate with contact time kill efficacies observed as a function of chain length with E. coli. The insights gained from our study uncover unexplored barrier properties of the bacterial cell envelope to rationalize the development of antimicrobial formulations and therapeutics.

We have investigated the permittivity and viscoelastic behavior of a binary system comprising bent-core and calamitic compounds, both of which are polar, the calamitic being more strongly so, and exhibiting only the nematic mesophase. The permittivity data in the nematic as well as the isotropic phase indicate strong polar interactions between the molecules, even for mixtures with a significant content of the bent-core compound. The thermal dependence of both the splay and bend elastic constants exhibit features different from the literature. The splay constant displays a large increase with increasing concentration of bent-core material, before undergoing a precipitous drop for small calamitic content materials. Upon lowering the temperature, certain mixtures exhibit a convex-shaped feature for the bend elastic constant; that is, the value of the elastic constant is maximum at a specific temperature in the nematic phase, diminishing when the temperature is either increased or decreased. Surprisingly, the pure compounds, especially the bent-core one, show only a monotonically increasing trend for the bend elastic constant. We present two arguments to explain these features: one of these is based on coupling between the molecular shape and director distortion presented in the literature. Then we put forth a new concept of frustration in the packing between the two types of molecules and the polar interactions as an alternative.