Tracking fast cellular membrane dynamics with sub-nm accuracy in the normal direction

Cellular membranes are important biomaterials with highly dynamic structures. Membrane dynamics plays an important role in numerous cellular processes, but precise tracking it is challenging due to the lack of tools with a highly sensitive and fast detection capability. Here we demonstrate a broad bandwidth optical imaging technique to measure cellular membrane displacements in the normal direction at sub-nm level detection limits and 20 μs temporal resolution (1 Hz-50 kHz). This capability allows us to study the intrinsic cellular membrane dynamics over a broad temporal and spatial spectrum. We measured the nanometer-scale stochastic fluctuations of the plasma membrane of HEK-293 cells, and found them to be highly dependent on the cytoskeletal structure of the cells. By analyzing the fluctuations, we further determine the mechanical properties of the cellular membranes. We anticipate that the method will contribute to the understanding of the basic cellular processes, and applications, such as mechanical phenotyping of cells at the single-cell level.