Mechanical regulation of nerve stem cells multiple behaviors via GHz acoustic streaming

Abstract

Mechanical regulation the behavior of neural stem cells is important for cellular transplantation and neural regenerative medicine, how neural stem cells perceive and respond to mechanical signals remains to be fully understood. In this study, a GHz bulk acoustic wave (BAW) resonator based acoustic streaming (AS) regulatory system was designed, aiming to use genegratetunable shear forces on the cells for regulating behaviors of neuroectodermal (NE-4C) stem cells. Results demonstrated that the gradient shear stress produced by AS had a regular regulation on cell movement, which could promote the movement model of cells transformed from pseudopodia into blebs-driven movement rapidly. Then, AS could improve the movement ability of cells by ~9.8 times than the unstimulated group. It was further proved that short-term AS stimulation could stably and efficiently promote both the parallel and vertical migration of cells. The number of vertically migrated cells in the 20 min group stimulated by AS was 10.9 times higher than that of the unstimulated group. Finally, the data showed that the proliferation multiple of cells could be controlled by changing the AS stimulation time and the input power of the device. In addition, AS stimulation could significantly accelerate the formation of neurite processes, and finally guide the production of neurons. To sum up, the AS shear force regulation system opened up the possibility of channelless microfluidic, which could easily manipulate the morphological changes of cells, provided a flexible tool for controllably regulating the migration, proliferation, and differentiation of neural stem cells, demonstrated its great potential in neural tissue engineering and regenerative medicine.