UCLA

Mechanical properties of cells and tissues play important roles in governing the behaviors of biological systems. Technologies for high-throughput quantification of multicellular mechanical responses provide fundamental insights into biological processes and are valuable in clinical applications, such as for diagnostics or drug discovery. Here, we present two different types of optical technologies for cell traction stress measurements over large fields-of-view of 0.6 mm2 and 13 mm2. The first type uses gold micro-disks or gold nanoparticles to scatter light strongly, thereby giving a high signal-to-noise ratio under dark field microscopy. This enables low magnification (10x) and low numerical aperture objective lenses to be used, hence greatly increasing the field-of-view over prior works whilst preserving sub-cellular resolution. The second type of optical technology are Diffractive Optical Tracers (DOT) for direct measurement of mechanical waves propagating over 10,000 interconnected cells with sub-cellular resolution over a field-of-view of 13 mm2. Dynamic mechanical stress distribution can be extracted from the color spectra recorded by an array of diffractive micromirrors embedded in an elastomer substrate. DOT provides mechanical information of individual cells, mechanical interactions between cells, patterns of traction stresses across multiple cells, and potential synergistic, antagonistic force generating activities. As a testbed example, we have applied DOT to measure the mechanical beating waves propagating through a syncytium of cardiomyocytes, quantify the dynamic contraction and relaxation forces of normal and phenylephrine treated neonatal rat ventricular myocytes (NRVMs). DOT can also be used to study other cell types including those derived from stem cells, cancer cells, macrophages, epithelial and endothelial cells for broad applications.