Nanodiamond-Based Spatial–Temporal Deformation Sensing for Cell Mechanics

Precise assessment of the mechanical properties of soft biological systems at the nanoscale is crucial for understanding physiology and pathology and developing relevant drugs. Conventional atomic force microscopy (AFM)-based indentation methods suffer from uncertainties in local tip–sample interactions and the model choice. This can be overcome by adopting spatially resolved nonlocal deformation sensing for mechanical analysis. However, the technique is currently limited to lifeless/static systems due to the inadequate spatial or temporal resolution or difficulties in differentiating the indentation-induced deformation from that associated with live activities and other external perturbations. Here, we develop a dynamic nonlocal deformation sensing approach allowing both spatially and temporally resolved mechanical analysis, which achieves a tens of microsecond time-lag precision, a nanometer vertical deformation precision, and a subhundred nanometer lateral spatial resolution. Using oscillatory nanoindentation and spectroscopic analysis, the method can separate the indentation-caused signal from random noise, enabling a live cell measurement. Using this method, we discover a distance-dependent phase of surface deformation during indentation, leading to the disclosure of surface tension effects (capillarity) in the mechanical response of viscoelastic materials and live cells upon AFM indentation. A viscoelastic model with surface tension is used to enable simultaneous quantification of the viscoelasticity and capillarity of the cell. We show that neglecting surface tension, as in conventional AFM methods, would underestimate the liquid-like characteristics and overestimate the apparent viscoelastic modulus of cells. This study provides exciting opportunities to understand a broad range of elastocapillarity-related interfacial mechanics and mechanobiological processes in live cells.