Researchers from the IRR Chemistry Hub have developed a new sensitive method that could transform the study of cell membrane disruption, a process linked to disease and antimicrobial resistance. Their innovative method, funded by the Leverhulme Trust, can help identify new drugs for diseases caused by membrane disruption, including Alzheimer’s, Parkinson’s, cancer and antimicrobial resistance. Cell membrane integrity is crucial for cell health, and when disrupted, is linked to diseases like Alzheimer’s, Parkinson’s, and cancer. The immune system also uses membrane disruption to fight off harmful pathogens. Testing the ability of compounds to disrupt cell membranes quickly is key to finding new drugs. 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 Mathew Horrocks IRR Group Leader To study membrane disruption by various compounds, researchers can use synthetic vesicles (bubble-like structures made from a single layer of lipids or ‘fats’), which mimic and integrate in natural cell membranes. Researchers can add fluorescent dyes to these vesicles which can report when and where the cell membranes break as the dye is released. However, these methods require high concentrations of compounds and often lack sensitivity.Microscopy methods can study individual vesicles with high precision, but they require giant vesicles which are challenging to work with under certain conditions. New techniques like single-molecule fluorescence microscopy have made it possible to study membrane disruption at a single-vesicle level. However, these methods often need vesicles to be immobilised on a surface, which can damage membranes and is time consuming. Image of a synthetic lipid vesicle made from a single layer of lipids or ‘fats’. They can mimic natural cell membranes, and be used to carry various compounds in its structure to allow for transport into and out of the lipid. This study introduces a new approach using ‘single-molecule confocal microscopy’ and ‘fast-flow microfluidics’ to study membrane disruption of synthetic lipid vesicles without needing to immobilise them. Their method is much faster and more sensitive than previous techniques, allowing for the study of even very small numbers of molecules. It can be used to test various compounds, including those related to antimicrobial resistance and neurodegenerative diseases like Parkinson’s disease. Their technology could be scaled up, facilitating high-throughput drug screening. This would allow for faster and more efficient research of drug targets, and has extensive applications in chemistry, biophysics, and medicine. In this work, we have designed a novel assay for the rapid determination of membrane permeabilization that can act 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 IRR Postdoctoral Researcher Read the full paper in Angewandte ChemistryIRR’s Chemistry HubHorrocks research group Tags CIR Publication date 10 Apr, 2025
