Mechanotransduction in hippocampal neurons operates under localized low picoNewton forces

There is growing evidence suggesting that mechanical properties of CNS neurons may play an important regulatory role in cellular processes. Here, we employ an oscillatory optical tweezers (OOT) to exert a local indentation with forces in the range of 5-50 pN. We found that single local indentation above a threshold of 13 ± 1 pN evokes a transient intracellular calcium change, whereas repeated mechanical stimulations induce a more sustained and variable calcium response. Importantly, neurons were able to differentiate the magnitude of mechanical stimuli. Chemical perturbation and whole-cell patch clamp recordings suggest that mechanically evoked response requires the influx of extracellular calcium through transmembrane ion channels. Moreover, we observed a mechanically evoked activation of the CAMKII and small G protein RhoA. These results all together suggest that mechanical signaling among developed neurons fully operates in neuronal networks under physiological conditions.