Understanding how Aβ42 oligomers induce changes in neurons from a mechanobiological perspective has important implications in neuronal dysfunction relevant to neurodegenerative diseases. However, it remains challenging to profile the mechanical responses of neurons and correlate the mechanical signatures to the biological properties of neurons given the structural complexity of cells. Here, we quantitatively investigate the nanomechanical properties of primary hippocampus neurons upon exposure to Aβ42 oligomers at the single neuron level by using atomic force microscopy (AFM). We develop a method termed heterogeneity-load-unload nanomechanics (HLUN), which exploits the AFM force spectra in the whole loading–unloading cycle, allowing comprehensive profiling of the mechanical properties of living neurons. We extract four key nanomechanical parameters, including the apparent Young’s modulus, cell spring constant, normalized hysteresis, and adhesion work, that serve as the nanomechanical signatures of neurons treated with Aβ42 oligomers. These parameters are well-correlated with neuronal height increase, cortical actin filament strengthening, and calcium concentration elevation. Thus, we establish an HLUN method-based AFM nanomechanical analysis tool for single neuron study and build an effective correlation between the nanomechanical profile of the single neurons and the biological effects triggered by Aβ42 oligomers. Our finding provides useful information on the dysfunction of neurons from the mechanobiological perspective.

In this work, we report that the effect of bioactive constituent on living glioma cells can be evaluated using terahertz time-domain attenuated total reflection (THz TD-ATR) spectroscopy in a label-free, non-invasive, and fast manner. The measured THz absorption coefficient of human glioma cells (U87) in cell culture media increases with ginsenoside Rg3 (G-Rg3) concentration in the range from 0 to 50 µM, which can be interpreted as that G-Rg3 deteriorated the cellular state. This is supported either by the cell growth inhibition rate measured using a conventional cell viability test kit or by the cellular morphological changes observed with fluorescence microscopy. These results verify the effectiveness of using the THz TD-ATR spectroscopy to detect the action of G-Rg3 on glioma cells in vitro. The demonstrated technique thus opens a new route to assessing the efficacy of bioactive constituents on cells or helping screen cell-targeted drugs.

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