A microfluidic device with spatiotemporal wall shear stress and ATP signals to investigate the intracellular calcium dynamics in vascular endothelial cells

Abstract

Intracellular calcium dynamics plays an important role in the regulation of vascular endothelial cellular functions. In order to probe the intracellular calcium dynamic response under synergistic effect of wall shear stress (WSS) and adenosine triphosphate (ATP) signals, a novel microfluidic device, which provides the adherent vascular endothelial cells (VECs) on the bottom of microchannel with WSS signal alone, ATP signal alone, and different combinations of WSS and ATP signals, is proposed based upon the principles of fluid mechanics and mass transfer. The spatiotemporal profiles of extracellular ATP signals from numerical simulation and experiment studies validate the implementation of our design. The intracellular calcium dynamics of VECs in response to either WSS signal or ATP signal alone, and different combinations of WSS and ATP signals have been investigated. It is found that the synergistic effect of the WSS and ATP signals plays a more significant role in the signal transduction of VECs rather than that from either WSS signal or ATP signal alone. In particular, under the combined stimuli of WSS and ATP signals with different amplitudes and frequencies, the amplitudes and frequencies of the intracellular Ca²⁺ dynamic signals are observed to be closely related to the amplitudes and frequencies of WSS or ATP signals.