Biophysical methods for monitoring cell-substrate interactions in drug discovery.

Cell-substrate interactions are implicated in a number of relevant pathways for drug targets such as angiogenesis, arteriosclerosis, chronic inflammatory diseases, and carcinogenesis. Moreover, cell adhesion and cytoskeletal activity have served as valuable indicators for cytotoxicity, cell density, and cell morphology. This review focuses on impedance, capacitance, resonant frequency, and refractive index measurements for monitoring cell adhesion in real time and without the use of cell labeling. ECIS, QCM, and OWLS deliver information about the cell-substrate interactions, cell-cell contact, and the strength of cell adhesion. Because of high sensitivity of these assays, events down to the single cell level have been observed, and resolutions at the nanometer level of cell-substrate distances have been achieved. The physical principles, including assay sensitivity and selectivity, are discussed in the context of cellular pathways of cell adhesion and migration. With the miniaturization of these types of sensors, cell migration and adhesion measurements in combination with specific fluorescent assays might thus deliver a high-content platform for drug development.