Microfluidic Analysis of Cell Communication and Nanomateial-Induced Stem Cell Differentiation

摘要

Our research interests have been focusing on the development of microfluidic device as a tool in studying cellular communication and performing high-throughput bioassays, and the understanding of the interaction mechanisms between nanomaterials and biological cells in order to control and manipulate these interactions for biomedical applications. In the first part of my talk, our recent work on microfluidic formation of single cell array for parallel analysis of ion channel activation and inhibition, and the development of a microfluidic platform to study suspension cell-cell communication will be presented. We have designed a microfluidic device consisting of parallel, independent channels with cell-docking structures for the formation of an array of individual cells. The microfluidic cell array was used to quantify single cell responses and the distribution of response patterns of calcium channels under the effects of specific activator and inhibitor molecules for a population of individual cells. We have also developed a microfluidic device for on-chip monitoring of suspension cell-cell communication under microvalve actuated mechanical stimulation. Different mechanical stimulation and flow environment were employed to study their impact on the behavior of cell-cell communication, including the duration and intensity of intracellular calcium responses and mediator release. These microfluidic devices may open up new avenues for real-time monitoring of suspension cell-cell communication, which propagates via gap-junction independent mechanism, with multiple variables under control. In the second part of my talk, I will introduce our recent work on the investigation of the cellular effects and the associated molecular mechanisms of nanomaterials on the modulation of mesenchymal stem cells (MSC) differentiation. The results showed that gold nano-particles AuNPs promoted the differentiation of MSCs towards osteoblast cells over adipocyte cells by interacting with the cell membrane and binding with proteins in the cytoplasma, causing mechanical stress on the MSCs to activate p38 mitogen activated protein kinase pathway (MAPK) signaling pathway, which regulates the expression of relevant genes to induce osteogenic differentiation and inhibit adipogenic differentiation. The interactions between carbon nanotubes and silicon nanowires with MSCs will also be discussed to illustrate the general mechanisms of how nanomaterials modulate the proliferation and differentiation of MSCs.