A paintbrush for delivery of nanoparticles and small molecules to live cells with micrometer spatial and millisecond temporal control

Abstract Delivery of very small amounts of reagents to cells with micrometer spatial precision and millisecond time resolution is currently out of reach, but would strongly facilitate quantitative studies in cell biology. Here, we present a micropipette-based scheme for brushing a layer of small molecules and nanoparticles onto the live cell membrane from a sub-femtoliter confined volume of a perfusion flow. We characterize our system through both experiment and model and find excellent agreement. We demonstrate several applications that benefit from a controlled brush delivery, such as a direct means to quantify local and long-range membrane mobility and organization as well as dynamical probing of intercellular force signaling.