Exploring Ultrasound-Induced Bubble-Cell Interaction Mechanisms at the Molecular Level: A joint Theory and Experiment Study – Bubble-Cell

The cavitation of microbubbles under ultrasound excitation generates hydrodynamic forces within the surrounding liquid, enhancing the permeability of biological barriers and enabling efficient delivery of therapeutic agents. This phenomenon forms the basis of sonoporation, a technique developed over the past three decades. Sonoporation has shown promise in delivering a wide range of therapeutics, both in vitro and in vivo studies. Several clinical trials targeting cancer, neurological disorders, and cardiovascular diseases are currently underway. However, despite these advances, sonoporation has yet to be widely adopted in clinical practice.
This project aims to address a persistent challenge in the field: the complex interplay between bubble cavitation and cellular response. A comprehensive understanding of the underlying mechanisms is essential for developing standardized protocols, which will allow for the optimization of ultrasound and microbubble parameters. This, in turn, will improve drug delivery efficacy, minimize side effects, and ultimately enhance the clinical applicability of sonoporation.
To achieve this, the project proposes two core aims: (i) develop an integrated framework combining computer simulations with cell mechanics experiments to investigate bubble-cell interactions at nano-micro spatiotemporal scales. (ii) Use this framework to elucidate the molecular mechanisms by which bubble cavitation enhances membrane permeability and drug internalization through cell deformation and pore formation.
Three partner institutions will contribute complementary expertise, covering all key aspects of bubble-induced cell permeabilization. The research strategy begins with the development of computational cell models, calibrated and validated using data from quasi-static and dynamic cell mechanics experiments In parallel, we will design novel microfluidic devices to enable precise investigation of microbubble cavitation and cellular responses at micrometer scale. A method for simulating bubble cavitation-cell interactions will also be developed.
Once the models and devices are established, a series of simulations and experiments will be conducted to explore bubble-cell interaction mechanisms. Key input parameters such as ultrasound and bubble parameters will be identified from the literature using machine learning techniques. Comparing simulation and experimental results will provide critical insights into: (i) the dynamics of microbubbles in acoustic fields and their associated hydrodynamic forces, (ii) cellular responses, including deformation and pore formation across spatial and temporal scales, and (iii) how these interactions impact drug delivery efficiency.
These insights will help explain the mechanisms, and the discrepancies between in vitro, in vivo, and theoretical studies, and clarify the variability in drug delivery outcomes reported in the literature. Furthermore, the computational framework and microfluidic devices will enable rapid exploration of the large parameter space in sonoporation, guiding experimental design and accelerating the development of ultrasound-based drug delivery technologies. Improved predictability, reduced drug dosage, fewer side effects, and lower medical waste will contribute to better therapeutic outcomes and lower healthcare costs.
Beyond scientific breakthroughs, the knowledge generated from simulation techniques to cellular mechanics and device design will be integrated into the MOOC on Therapeutic Ultrasound at the Lyon University, making cutting-edge research accessible to students, scientists, and healthcare professionals worldwide.