Smart bio-MEMS for cell mechanics studies

Abstract

As our inquiry into different biological and cellular processes deepens, a wide range of simulation and engineering tools become increasingly popular. In particular, because of their miniature size, precisely controlled micro-topology and operation accuracy, microelectronicmechanical systems (MEMS) have been widely used in various biomedical investigations in the past few decades. In this study, we report our efforts in developing different MEMS-based devices to interrogate cellular migration, enforced deformation, and signal transmission at the single-cell level.First, we utilized MEMS to examine topography-assisted migration of cells. Specifically, precisely controlled undulation amplitude and wavelength were introduced to the wall of microchannels. The movement of immune cells trapped inside such channels was then carefully monitored. Interestingly, it was found that persistent cellular movement can be achieved in undulated microchannels even without cell-channel adhesion. Furthermore, the migration speed of cells was observed to reach its maximum under intermediate undulation amplitude and wavelength values, irrespective of the actual geometry of the surface undulation. Our myosin inhibition experiment and theoretical modelling showed that the retrograde actin flow, induced by active myosin contraction, is thwarted by the serrated channel wall, which effectively provides the friction force for cells to move. Next, a bio-MEMS device was designed and fabricated to characterize the mechanical and electrical properties of cells. Specifically, an array of trapping units was introduced in the microfluidic chip for the immobilization cells. After that, flow-induced compression was applied to trapped cells to cause their deformations. With the help of a customized computer vision algorithm, segmentation, geometric measurement and subsequent extraction of viscoelastic characteristics of cells can all be realized automatically. Furthermore, by embedding micro-electrodes beneath each trapping unit, the electrical property of cells is also probed via electric impedance spectroscopy. Compared to conventional methods, where mechanical and electrical responses are often investigated separately, our approach simultaneously characterises these two properties. In addition, the fact that tens/hundreds of cells can be measured in our system gives it a higher throughput than existing single-cell mechanical characterization methods. Finally, we investigated force-regulated signal transmission in neurons. Specifically, we showed that mechanical compression beyond a threshold level can trigger calcium response in neural cells due to the force-sensitive behaviour of TRPV1 and TRPV4 channels. In addition, a microfluidic chip enabling the formation of neuron junctions over a gap region was developed first. A micromechanical stage, with a carefully designed load-deflection relationship, was fabricated via 3D printing to provide mechanical support for the chip. Effectively, the stage will serve as a loading device, allowing us to apply precisely controlled force on the cell-cell junction. By introducing precisely controlled electric or chemical stimuli on the presynaptic side, the responding signals in postsynaptic neurons under different applied tensions on the synaptic junction can then be quantitatively monitored for the first time.