Probing Cell Mechanotransduction and Electric Activity with Microfluidic Platforms

Abstract

How cells detect and respond to mechanical, chemical, and electrical stimuli and make vital cellular decisions accordingly has been extremely puzzling and intriguing. Despite unremitting efforts of generations of researchers, there are still many mysteries remaining to be addressed, partly due to the limitations of available technologies. In this work, a series of novel microfluidic platforms were developed and applied to the studies of cell mechanotransduction and electrical activities as well as organism behaviors. First, experiments based on a microfluidic stretcher device demonstrates a key role of mechanical stretching and relaxation in normal fibroblasts (NAFs) activation and cancer-associated fibroblasts (CAFs) deactivation, indicating a new potential cancer therapeutic strategy targeting tumor stroma. In addition, a three-dimensional (3D) compression assay illustrates significantly different orientation behavior of NAFs and CAFs in response to 3D compression. Such distinction was understood based on the significant difference of the inherent stress generated by stress fibers, a major intercellular machinery, between NAFs and CAFs. For electrical activity studies, a novel graphene-based microfluidic platform was constructed to probe the electrical signals of individual dendritic spines and synaptic contacts in the central nervous systems. Ultrahigh spatiotemporal resolution of the graphene-transistor based scanning photocurrent microscopy has been demonstrated. Finally, new microfluidic platforms have also been developed to study organism behaviors. A microfluidic diode structure was created for facilitating C. elegans translocation, based on which a collection of devices was designed for simultaneous worm sorting at a high throughput as well as collection or immobilization for further investigation. In summary, this dissertation showcased a class of novel microfluidic platforms and demonstrated important biological applications spanning subcellular, cellular, and organismal levels.