Picture this: You're at a party, and everyone is wearing bright neon-colored jackets. No, you're not back in the 1980s—you're fluorescently labeled Escherichia coli trapped in a microfluidic device. We designed this flamboyant scene to study how cells handle pressure, in part by staining each unique cell type (strain) with a distinct vibrant fluorescent dye. This allowed us to test many strains at once, resulting in better-controlled experiment-to-experiment variability, while saving us precious time and resources. That’s our party of discovery, which we call "Disco-li."
How these partygoers handle pressure is partly because of a structure that surrounds the cell, known as the outer membrane. This membrane is a mechanical marvel, which bends, stretches, blebs, and resists squishing or popping, all while performing essential physiological functions. Our latest work used a novel biophysics assay to answer the question “What keeps the outer membrane intact under compression?” It turns out that membrane constituents, such as proteins and lipo-sugars, act as critical reinforcements. Surprisingly, when we removed both, the membrane was stiffer than if only a single component was removed. This counterintuitive phenomenon, known as "sign epistasis," probably results from how different membrane constituents interact and partition, depending on which component was removed.
This biological and mechanical complexity not only rouses scientific curiosity but also has far-reaching real-world implications. The outer membrane acts as a formidable permeability barrier, even for our most effective antibiotics. By studying outer membrane mechanics, we are mapping its structural supports—much like pinpointing the load-bearing walls of a building to target during demolition. This could lead to new drugs that breach this barrier, offering hope in the fight against antibiotic-resistant superbugs. Beyond antibiotic resistance, we hope that our disco-like color-coding will prove a useful, time-saving technique for microbiology laboratories spanning many fields.
To learn more about our other exciting projects, visit our websites https://rojaslab.com/ and https://www.dylanfitzmaurice.com/.
— Dylan R. Fitzmaurice, Anthony Amador, Tahj Starr, Glen M. Hocky, and Enrique R. Rojas