Mechano-sensitization of mammalian neuronal networks through expression of the bacterial mechanosensitive MscL channel

Abstract

Development of remote stimulation techniques for neuronal tissues represents a challenging goal. Among the potential methods, mechanical stimuli are the most promising vector to convey information non-invasively into intact brain tissue. In this context, selective mechano-sensitization of neuronal circuits would pave the way to develop a new cell-type specific stimulation approach. We report here for the first time the development and characterization of mechano-sensitized neuronal networks through the heterologous expression of an engineered bacterial large conductance mechanosensitive ion channel (MscL). The neuronal functional expression of the MscL channel was validated through patch-clamp recordings upon application of calibrated suction pressures. Moreover, we verified the effective development of in-vitro neuronal networks expressing the engineered MscL channel in terms of cell survival, number of synaptic puncta, and spontaneous network activity. The pure mechanosensitivity of the engineered MscL channel, with its wide genetic modification library, may represent a versatile tool to further develop a mechano-genetic approach.