Picofluidic Electro‐Osmosis Measurement of Cell Membrane Mechanical Properties

Abstract Cells connect with their internal and external environments through plasma membranes, and the mechanical properties of cell membranes govern numerous biological events. Membrane detection techniques such as optical or magnetic tweezers have revealed mechanical strength by membrane‐anchored modifications, but it remains challenging to develop label‐free methods to reduce the influence of exogenous interference. Here picofluidic electro‐osmosis measurement (PEOM), which enables direct and efficient sensing of cell membrane mechanical properties by using a glass nanopipette without labeling, is presented. By generating a picoliter electroosmotic fluid at the nanopipette tip, periodic cell membrane vibration modes are observed from current traces, which carry information on membrane mechanical properties to indicate its biological state. Based on characteristic peaks in the frequency domain, a theoretical framework to describe the vibration modes, which contains two ideal spring vibrator models corresponding to stretching and bending vibrations of cell membrane respectively, is developed. Notably, the PEOM strategy represents a label‐free approach to reveal the mechanical properties of living cell membranes from two dimensions, which is completely different from other methods. Additionally, the exciting potential of PEOM is demonstrated for label‐free observation of membrane mechanical property changes during different bioprocesses, including cytoskeletal alteration, membrane tension change, and mechanical polarization.