An experimental study on the apparent stiffness of size-isolated microbubbles used for blood-brain barrier opening applications

In order to fully assess contrast-enhanced acoustic bioeffects in diagnostic and therapeutic applications, the mechanical properties of microbubbles need to be taken into account. In the current study, direct measurements of the microbubble apparent stiffness were performed using atomic force microscopy by applying nanoscale compressions (up to 25 nN/s) on size-isolated, phospholipid-coated microbubbles (diameters between 4-6 and 6-8 μm). The apparent stiffness was found to lie between 4 and 22 mN/m and to decrease exponentially with microbubble size within the diameter range investigated. No cantilever spring constant effect was found on the measured stiffness. The Young´s modulus of the sizeisolated microbubbles used in our study ranged between 0.4 and 2 MPa. Microstructures on the surface of the microbubbles were found to influence the overall microbubble elasticity. Our results indicated that more detailed theoretical models are needed to account for the size-dependent microbubble mechanical properties in order to accurately predict their acoustic behavior. The findings provided useful insights to control cavitation-induced drug and gene delivery and could be used as part of the framework in studies on the shear stresses induced on the blood vessel walls by the oscillating microbubbles.