Addressing Challenges in Fluid Flow-Induced Cell Membrane Oscillation by Nanopipettes.

The mechanical properties of cell membranes are crucial to regulating cell morphology and behavior. Nanopipette-sensing has become distinctively appealing for the measurement of cell membrane mechanical properties due to its label-free operation and precise targeting. Recent progress has involved precise control of the movement and fluid flow of the nanopipet, which can induce cell membrane oscillation. However, it remains challenging to trigger and interpret the membrane oscillation signals due to the complex interaction between electroosmotic flow, membrane movement, and cell endurance. Here, we investigated the fluid flow at the orifice of nanopipettes with different tip diameters and its influence on triggering periodic membrane oscillation of single living cells. Experimental results and simulations through delicate control of chemical, physical, and electronic parameters suggested the critical role of electroosmosis in driving fluid low and generating cell membrane oscillation. We also showed that nanopipettes with a tip diameter of around or less than 100 nm do not exhibit obvious damage to living cells. Our findings elucidate the fundamental prerequisites for measuring cell membrane mechanical properties by nanopipettes and provide an in-depth understanding for the interactions between nanopipettes and cell membranes.