Researchers from the Horrocks and Cockroft groups have developed a single-molecule liposome assay that promises to transform the study of cell membrane disruption by proteins and peptides. Their innovative method, funded by the Leverhulme Trust, addresses longstanding challenges in membrane-related research across antimicrobial activity, toxicity, and disease pathology. Membrane integrity is crucial for cellular health, playing a vital role in processes such as ion transport and signal transmission. Disruption of these membranes is linked to various disorders, including Alzheimer's and Parkinson’s disease, and certain cancers. Traditional techniques for examining the membrane-disrupting effects of proteins and peptides can be challenging and often require larger quantities, which are costly and difficult to produce. This new approach uses single-molecule confocal microscopy with fast-flow microfluidics to detect membrane disruption with minimal quantities of proteins and peptides. This method provides unparalleled sensitivity, allowing for the observation of individual molecular events without the need for ensemble averaging. This means researchers can capture molecular heterogeneity and subtle variations that are often lost in bulk measurements. The technology is scalable and supports high-throughput parallelisation, making it suitable for extensive applications in chemistry, biophysics, and medicine.Professor Mathew Horrocks, senior author, says The new approach enables rapid screening of compounds capable of disrupting or permeabilising biological membranes. We’ve traditionally used single-molecule approaches to simply look at biological systems, and so it’s exciting that we’ve now developed a method that can measure the function of biomolecules. We anticipate that our technique will streamline the development of new therapeutics and enhance our understanding of membrane dynamics in health and disease. Professor Matthew Horrocks Personal Chair of Biophysics, School of Chemistry, University of Edinburgh In this work, we have designed a novel assay for the rapid determination of membrane permeabilization that can act as a biological mimic to study a huge variety of anti-microbial, channel-forming, and ion-transporting mechanisms. Our assay utilises single-molecule confocal microscopy equipped with a microfluidic device which affords outstanding limits of detection and minimises the amount of material required to study the activity of an analyte. Dr Dan Edwards Postdoctoral Research Associate, School of Chemistry, University of Edinburgh Read the paper in Angewandte Chemie International Edition: https://onlinelibrary.wiley.com/doi/10.1002/anie.202503678 Find out more about Horrocks and Cockroft Group research: https://www.horrockslab.org https://chem.ed.ac.uk/cockroft-group Publication date 11 Apr, 2025
