A Nano-Anchor for Anti-Drift Vesicle Imaging.

Microscopic imaging remains the primary strategy for studying naturally-derived or biomimetic membrane systems. Long-term tracking requires both a stable three-dimensional focal plane and minimal target displacement. This poses a significant challenge for non-adherent cells or vesicles that tend to migrate due to gravity, temperature fluctuation, air flow, and environmental vibration. Herein, we present a non-destructive immobilization technique, using glutaraldehyde-modified UiO-66-NH2 nanoparticles as anchors to prevent drifting of membrane systems. Demonstrated using a giant unilamellar vesicles (GUVs) model that features cell-like morphology and adjustable membrane lipid composition, the uniform anchoring modification retains membrane structural integrity and fluidity-related properties, including vesicle self-deformation and fusion between oppositely charged GUVs. The nano-anchor enables rapid immobilization of GUVs and semi-adherent cells on glass slides within 5 min under ambient conditions. Furthermore, this technology is well-suited for imaging applications that require high stability and precision, as evidenced by photobleaching recovery analysis and 3D reconstructions of lipid raft microdomains. Therefore, the anti-drift nano-anchor approach facilitates versatile studies across on-membrane and intermembrane processes.