Nanodevices to Measure Cell Mechanics

In the human body, the mechanical aspects of cell matrices are critical in maintaining cell differentiation and growth patterns. Both the static rigidity of the matrix and the stretching activity of the matrix are critical factors. Using PDMS pillars of submicrometer diameters, we first determined that the static rigidity of the matrix was measured by local contractions of 100 nm by sarcomere-like units of about 2 micrometers (Wolfenson et al., 2016).  These modular rigidity-sensing machines contained many cytoskeletal proteins like tropomyosin, a-actinin, actin and myosin. When they were missing, cells did not sense soft surfaces and grew inappropriately. When rigidity sensors were present, cells would die on soft surfaces but growth was rescued if the soft surfaces were stretched. 1-5% cyclic stretching over a frequency range of 0.01 to 10 Hz caused spreading and growth (optimum 0.1 Hz) (Cui et al., 2015). Of possible factors linked to fibroblast growth, MRTF-A (Myocardin-related transcription factor-A) moved to the nucleus in 2 hrs of cyclic stretching and reversed upon cessation; but, YAP (Yes-associated protein) moved much later. Knockdown of either MRTF-A or YAP blocked stretch-dependent growth. Thus, we suggest that the repeated pulling from a soft matrix can substitute for a stiff matrix in stimulating spreading and growth.  More generally, mechanical activation of cell substrates can be used to control cell growth and even differentiation.