Sloan, S. P.; Pattinson, O.; Ben Issa, A. A.; Stride, E.; Tilley, S.; Kanczler, J.; Carugo, D.; Pierron, F.; Evans, N. D.

Ultrasound-stimulated microbubbles can transiently permeabilise cells and enhance targeted therapeutic delivery, yet clinical efficacy varies markedly across tissues with distinct mechanical properties. How cellular material properties govern microbubble-cell interactions under megahertz-rate loading - far beyond the frequency range accessible to conventional cell mechanobiology - remains unresolved, limiting control of sonoporation. Here we combine ultra-high-speed imaging with digital image correlation to resolve the propagation of microbubble-induced deformation at megahertz frequencies in living cells. Microbubble oscillations generate harmonic mechanical waves whose spatial decay defines a micrometre-scale attenuation length governed by cytoskeletal organisation and intracellular viscoelastic dissipation. Perturbing cytoskeletal mechanics determines deformation propagation distance and deformation wave speed, which in parallel alters permeabilisation efficiency in both tumour-derived and primary human bone-marrow stromal cells. These findings identify intracellular viscoelasticity as a determinant of microbubble bioeffects at ultrasound rates and position tissue mechanical state as a design parameter for optimising ultrasound-mediated therapeutic delivery.