Evaluating the Structural Response of Amphiphilic Monolayers to Environmental Stimuli.

Amphiphilic monolayers composed of end groups with distinct polar and nonpolar functional groups offer rapid and reversible interfacial adaptation in response to environmental stimuli such as a change in interfacial medium polarity. We have synthesized and characterized a suite of monolayers with functional groups of competing polarity designed to reconfigure their interfacial chemical composition in response to solvent polarity. In these films, the end group is designed to be able to reorient and expose the functional groups that minimize the interfacial free energy between the film and the environment.

Probing bacterial membranes with polarization-resolved second harmonic scattering.

For antibiotics that target Gram-positive bacterial cell structures, optimizing their interaction with the cytoplasmic membrane is of paramount importance. Recent time-resolved second harmonic scattering (trSHS) experiments with living bacterial cells have shown that some amphiphilic small molecules display signals consistent with organization within the membrane environment. Such organization could arise, for example, from aggregation, solvent interactions, and/or environmental rigidity.

Miltefosine impacts small molecule transport in Gram-positive bacteria.

Miltefosine (MLT) is an alkylphosphocholine with clinical success as an anticancer and antiparasitic drug. Although the mechanism of action of MLT is highly debated, the interaction of MLT with the membrane, specifically lipid rafts of eukaryotes, is well-documented. Recent reports suggest MLT impacts the functional membrane microdomains in bacteria - regions of the membrane structurally and functionally similar to lipid rafts.

Facilitating flip-flop: Structural tuning of molecule-membrane interactions in living bacteria.

The first barrier that a small molecule must overcome before trespassing into a living cell is the lipid bilayer surrounding the intracellular content. It is imperative, therefore, to understand how the structure of a small molecule influences its fate in this region. Through the use of second harmonic generation, we show how the differing degrees of ionic headgroups, conjugated system, and branched hydrocarbon tail disparities of a series of four styryl dye molecules influence the propensity to "flip-flop" or to be further organized in the outer leaflet by the membrane.

Monitoring membranes: The exploration of biological bilayers with second harmonic generation.

Nature's seemingly controlled chaos in heterogeneous two-dimensional cell membranes stands in stark contrast to the precise, often homogeneous, environment in an experimentalist's flask or carefully designed material system. Yet cell membranes can play a direct role, or serve as inspiration, in all fields of biology, chemistry, physics, and engineering. Our understanding of these ubiquitous structures continues to evolve despite over a century of study largely driven by the application of new technologies.

Phosphate Ions Alter the Binding of Daptomycin to Living Bacterial Cell Surfaces.

Advancements in antibiotic drug design are often hindered by missing information on how these small molecules interact with living cells. The antibiotic, daptomycin, has found clinical success and an emerging resistance, but a comprehensive picture of its mechanism of action has remained elusive. Using a surface-specific spectroscopy technique, second harmonic generation, we are able to quantitatively assess the binding of daptomycin to living cell membranes without the addition of exogenous labels.

Leaving the Limits of Linearity for Light Microscopy.

Nonlinear microscopy has enabled additional modalities for chemical contrast, deep penetration into biological tissues, and the ability to collect dynamics on ultrafast timescales across heterogenous samples. The additional light fields introduced to a sample offer seemingly endless possibilities for variation to optimize and customize experimentation and the extraction of physical insight. This perspective highlights three areas of growth in this diverse field: the collection of information across multiple timescales, the selective imaging of interfacial chemistry, and the exploitation of quantum behavior for future imaging directions.