Cui Yue, Leong Weng-Hang, Zhu Guoli, Liu Ren-Bao, Li Quan
Department of Physics, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong 999077, China.
Quantum Science Center of Guangdong-Hong Kong-Macao Greater Bay Area (Guangdong), Shenzhen 518045, China.
ACS Nano. 2025 Apr 15;19(14):13740-13751. doi: 10.1021/acsnano.4c15003. Epub 2025 Apr 2.
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.
在纳米尺度上精确评估软生物系统的力学性能对于理解生理学和病理学以及开发相关药物至关重要。传统的基于原子力显微镜（AFM）的压痕方法存在局部针尖-样品相互作用和模型选择方面的不确定性。通过采用空间分辨的非局部变形传感进行力学分析可以克服这一问题。然而，由于空间或时间分辨率不足，或者难以区分压痕引起的变形与与生命活动和其他外部扰动相关的变形，该技术目前仅限于无生命/静态系统。在此，我们开发了一种动态非局部变形传感方法，允许进行空间和时间分辨的力学分析，该方法实现了数十微秒的时间滞后精度、纳米级的垂直变形精度和亚百纳米级的横向空间分辨率。使用振荡纳米压痕和光谱分析，该方法可以将压痕引起的信号与随机噪声分离，从而实现活细胞测量。使用该方法，我们发现了压痕过程中表面变形的距离依赖性阶段，从而揭示了粘弹性材料和活细胞在AFM压痕时力学响应中的表面张力效应（毛细作用）。使用具有表面张力的粘弹性模型可以同时量化细胞的粘弹性和毛细作用。我们表明，像传统AFM方法那样忽略表面张力会低估细胞的类液体特性，并高估细胞的表观粘弹性模量。这项研究为理解活细胞中广泛的弹性毛细作用相关界面力学和力学生物学过程提供了令人兴奋的机会。
