Non-invasive monitoring of single-cell mechanics by acoustic scattering

Monitoring mechanics of the same cell throughout the cell cycle has been hampered by the invasiveness of mechanical measurements. Here, we quantify mechanical properties via acoustic scattering of waves from a cell inside a fluid-filled vibrating cantilever with a temporal resolution of <1 min. Through simulations, experiments with hydrogels and chemically perturbed cells, we show that our readout, the size-normalized acoustic scattering (SNACS), measures stiffness. We demonstrate the noninvasiveness of SNACS over successive cell cycles using measurements that result in < 15 nm deformations. Cells maintain constant SNACS throughout interphase but exhibit dynamic changes during mitosis. Our work provides a basis for understanding how growing cells maintain mechanical integrity and demonstrates that acoustic scattering can non-invasively probe subtle and transient dynamics.