Flow-induced stress on adherent cells in microfluidic devices

Transduction of mechanical forces and chemical signals affect every cell in the human body. Fluid flow in systems such as the lymphatic or circulatory systems modulates not only cell morphology, but also gene expression patterns, extracellular matrix protein secretion and cell-cell and cell-matrix adhesions. Similar to the role of mechanical forces in adaptation of tissues, shear fluid flow orchestrates collective behaviours of adherent cells found at the interface between tissues and their fluidic environments. These behaviours range from alignment of endothelial cells in the direction of flow to stem cell lineage commitment. Therefore, it is important to characterize quantitatively fluid interface-dependent cell activity. Common macro-scale techniques, such as the parallel plate flow chamber and vertical-step flow methods that apply fluid-induced stress on adherent cells, offer standardization, repeatability and ease of operation. However, in order to achieve improved control over a cell's microenvironment, additional microscale-based techniques are needed. The use of microfluidics for this has been recognized, but its true potential has emerged only recently with the advent of hybrid systems, offering increased throughput, multicellular interactions, substrate functionalization on 3D geometries, and simultaneous control over chemical and mechanical stimulation. In this review, we discuss recent advances in microfluidic flow systems for adherent cells and elaborate on their suitability to mimic physiologic micromechanical environments subjected to fluid flow. We describe device design considerations in light of ongoing discoveries in mechanobiology and point to future trends of this promising technology.