基于纳米金刚石的细胞力学时空形变传感
Nanodiamond-based spatial-temporal deformation sensing for cell mechanics
AI总结：
针对传统AFM压痕法的不确定性及现有非局部形变传感无法用于活细胞的问题，开发了时空分辨的动态非局部形变传感方法，发现活细胞压痕响应中的表面张力效应，为相关力学与生物学研究奠定基础。
摘要：
在纳米尺度上精确评估软生物系统的力学特性，对于理解生理、病理过程以及开发相关药物至关重要。传统基于原子力显微镜（AFM）的压痕方法存在针尖-样品局部相互作用及模型选择的不确定性问题，采用空间分辨的非局部形变传感进行力学分析可克服这一缺陷。但目前该技术受限于空间或时间分辨率不足，以及难以区分压痕诱导的形变与生命活动、其他外部扰动相关的形变，仅适用于无生命/静态系统。\n本文开发了一种创新的动态非局部形变传感方法，可实现时空分辨的力学分析，达到数十微秒的时间滞后精度、纳米级垂直形变精度以及亚百纳米的横向空间分辨率。该方法结合振荡纳米压痕与光谱分析，可将压痕产生的信号与随机噪声分离，从而实现活细胞测量。利用该方法，我们发现压痕过程中表面形变存在距离依赖的相位，进而揭示了活细胞在AFM压痕下的力学响应中存在表面张力效应（毛细作用）。通过引入含表面张力的粘弹性模型，可同时量化细胞的粘弹性与毛细作用。研究表明，传统AFM方法忽略表面张力，会低估细胞的类液体特性，高估细胞的表观粘弹性模量。本研究为理解活细胞中广泛的弹性毛细相关界面力学及力学生物学过程奠定了基础。
英文摘要：
Precise assessment of the mechanical properties of soft biological systems at the nanoscale is crucial for understanding physiology, pathology, and developing relevant drugs. Conventional atomic force microscopy (AFM)-based indentation methods suffer from uncertainties in local tip-sample interactions and 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 an innovative 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 sub-hundred nanometer lateral spatial resolution. Using oscillatory nanoindentation and spectroscopic analysis, the method can separate the indentation-caused signal from random noise, enabling 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 live cells upon AFM indentation. A viscoelastic model with surface tension is used to enable simultaneous quantification of the viscoelasticity and capillarity of 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. The study lays down a foundation for understanding a broad range of elastocapillarity-related interfacial mechanics and mechanobiological processes in live cells.
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