Nanomechanical Profiling of A beta 42 Oligomer- Induced Biological Changes in Single Hippocampus Neurons

Understanding how A beta 42 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 hippo campus neurons upon exposure to A beta 42 oligomers at the single neuron level by using atomic force microscopy (AFM). We develop a method termed heterogeneity-load-unload nano mechanics (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 A beta 42 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 A beta 42 oligomers. Our finding provides useful information on the dysfunction of neurons from the mechanobiological perspective.