Real‐Time Quantification of Cell Mechanics and Functions by Double Resonator Piezoelectric Cytometry – Theory and Study of Cellular Adhesion of HUVECs

Abstract Cell mechanics is closely associated with cellular structure and function. However, the inability to measure both cellular force and viscoelasticity of statistically significant number of cells noninvasively remains a challenge for quantitative characterizations of various cellular functions and practical applications. Here a double resonator piezoelectric cytometry (DRPC), using AT and BT cut quartz crystals of the same frequency and surface morphology is developed to simultaneously quantify the cells‐generated forces (ΔS) and viscoelastic moduli (G′, G″) of a population of isolated single cells or cells with different degrees of cell‐cell interactions in a non‐invasive and real time manner. DRPC captures the dynamic mechanical parameters ΔS and G′, G″ during the adhesions of human umbilical vein endothelial cells (HUVECs) under different ligand densities of adhesion molecules fibronectin or Arg‐Gly‐Asp (RGD) modified on the gold surfaces of 9 MHz AT and BT cut quartz crystals, and different seeding densities of HUVECs. It is found that both the ligand density and cell seeding density affect the magnitudes of ΔS and G′, G″ and their correlations are revealed for the first time by DRPC. The validity of DRPC is further verified by mechanical changes of the cells in response to treatments with cytoskeleton regulators.