MXene energy transfer for single-molecule leaflet-resolved sensing in model lipid bilayers – MEXSENS

MEXSENS introduces 2D titanium carbide MXenes as powerful nanoscale sensors for single-molecule fluorescence studies of supported lipid bilayers, providing unprecedented leaflet-resolved precision. These nanomaterials, acting as spectroscopic nanorulers, exhibit exceptional sensitivity to lipid heterogeneities within the confined membrane space. By leveraging distance-dependent MXene energy transfer (MXET), fluorescent molecules are precisely localized at distances of 1 to 10 nm, enabling nanoscale discrimination of lipid bilayer leaflets at the single-molecule level. This surpasses other materials in terms of sensitivity, robustness, and membrane compatibility. The MEXSENS project aims to detect nanoscale membrane heterogeneities arising from small molecule interactions, offering new insights into lipid behavior with critical implications for drug discovery and membrane biophysics. While leaflet discrimination has been successfully demonstrated, key challenges remain, including the fabrication of uniform sensor films and the creation of stable asymmetric lipid bilayers, essential for realistic plasma membrane models. Addressing these challenges will advance MXET technology for studying small molecule-lipid interactions and detecting subtle molecular binding dynamics with high precision. This approach will pave the way to high-throughput multimodal sensors, uncovering previously undetectable lipid heterogeneities for both biophysical research and drug discovery.