Understanding the mechanical properties of cells requires quantitative, time-resolved techniques adapted to non-adherent biological objects. I will present developments around a profile microindentation technique combining flexible glass microindenters, optical position tracking, and piezo-based force feedback.

I will show how this approach:

- reveals spontaneous stiffness oscillations in resting CD4+ T cells (~30 s period) driven by actomyosin cortex dynamics,

- uncovers a photostiffening effect — fluorescence excitation causes rapid, irreversible cell stiffening mediated by reactive oxygen species, independent of actin integrity and observed across multiple cell types,

- enables quantifying the wall mechanics of coccidian parasite oocysts,

- opens new perspectives on CAR-T cell mechanics and how engineered immune cells differ from primary T cells, with implications for therapeutic efficacy.