Pierron, F. | bioRxiv Science

bioRxiv2026

The material properties of the cell determine microbubble-induced cell deformation and permeabilisation

Mechanical properties influence how cells withstand and transmit force, but their role in clinically relevant, high-frequency therapeutic perturbations remains poorly understood. Ultrasound-stimulated microbubbles can locally deform cells and tissues to enhance drug delivery, yet therapeutic responses vary markedly across mechanical microenvironments. How cellular material properties govern microbubble-cell interactions at megahertz loading rates - well beyond the range accessible to conventional mechanobiology - remains unresolved. Here we combine ultra-high-speed imaging with digital image correlation to map microbubble-induced deformation in living cells at ultrasound frequencies. We show that oscillating microbubbles generate harmonic deformation waves whose spatial decay defines a micrometre-scale attenuation length governed by cytoskeletal organisation and intracellular viscoelastic dissipation. Pharmacological softening or stiffening alters both deformation propagation and wave speed, and these mechanical changes predict permeabilisation efficiency in tumour-derived and primary human bone-marrow stromal cells. These findings establish cellular viscoelasticity as a determinant of microbubble bioeffects and suggest that tissue mechanical state can be used as a design parameter for ultrasound-mediated therapeutic delivery.

bioengineering↗

bioRxiv2023

The image-based ultrasonic cell shaking test

Mechanical signals play a vital role in cell biology and is a vast area of research. Thus, there is motivation to understand cell deformation and mechanobiological responses. However, the ability to controllably deform cells in the ultrasonic regime and test their response is a noted challenge throughout the literature. Quantifying and eliciting an appropriate stimulus has proven to be difficult, resulting in methods that are either too aggressive or oversimplified. Furthermore, the ability to gain a real-time insight into cell deformation and link this with the biological response is yet to be achieved. One application of this understanding is in ultrasonic surgical cutting, which is a promising alternative to traditional methods, but with little understanding of its effect on cells. Here we present the image based ultrasonic cell shaking test, a novel method that enables controllable loading of cells and quantification of their response to ultrasonic vibrations. Practically, this involves seeding cells on a substrate that resonates at ultrasonic frequencies and transfers the deformation to the cells. This is then incorporated into microscopic imaging techniques to obtain high-speed images of ultrasonic cell deformation that can be analysed using digital image correlation techniques. Cells can then be extracted after excitation to undergo analysis to understand the biological response to the deformation. This method could aid in understanding the effects of ultrasonic stimulation on cells and how activated mechanobiological pathways result in physical and biochemical responses.

bioengineering↗