Selective flow-induced vesicle rupture to sort by membrane mechanical properties

International audienceVesicle and cell rupture caused by large viscous stresses in ultrasonication is central to biomedical and bioprocessing applications. The flow-induced opening of lipid membranes can be exploited to deliver drugs into cells, or to recover products from cells, provided that it can be obtained in a controlled fashion. Here we demonstrate that differences in lipid membrane and vesicle properties can enable selective flow-induced vesicle break-up. We obtained vesicle populations with different membrane properties by using different lipids (SOPC, DOPC, or POPC) and lipid:cholesterol mixtures (SOPC:chol and DOPC:chol). We subjected vesicles to large deformations in the acoustic microstreaming flow generated by ultrasound-driven microbubbles. By simultaneously deforming vesicles with different properties in the same flow, we determined the conditions in which rupture is selective with respect to the membrane stretching elasticity. We also investigated the effect of vesicle radius and excess area on the threshold for rupture, and identified conditions for robust selectivity based solely on the mechanical properties of the membrane. Our work should enable new sorting mechanisms based on the difference in membrane composition and mechanical properties between different vesicles, capsules, or cells

Surface waves on a soft viscoelastic layer produced by an oscillating microbubble

Ultrasound-driven bubbles can cause significant deformation of soft viscoelastic layers, for instance in surface cleaning and biomedical applications. The effect of the viscoelastic properties of a boundary on the bubble-boundary interaction has been explored only qualitatively, and remains poorly understood. We investigate the dynamic deformation of a viscoelastic layer induced by the volumetric oscillations of an ultrasound-driven microbubble. High-speed video microscopy is used to observe the deformation produced by a bubble oscillating at 17-20 kHz in contact with the surface of a hydrogel. The localised oscillating pressure applied by the bubble generates surface elastic (Rayleigh) waves on the gel, characterised by elliptical particle trajectories. The tilt angle of the elliptical trajectories varies with increasing distance from the bubble. Unexpectedly, the direction of rotation of the surface elements on the elliptical trajectories shifts from prograde to retrograde at a distance from the bubble that depends on the viscoelastic properties of the gel. To explain these behaviours, we develop a simple three-dimensional model for the deformation of a viscoelastic solid by a localised oscillating force. By using as input for the model the values of the shear modulus obtained from the propagation velocity of the Rayleigh waves, we find good qualitative agreement with the experimental observations

Shear-induced deformation of surfactant multilamellar vesicles

Surfactant multilamellar vesicles (SMLVs) play a key role in the formulation of many industrial products, such as detergents, foodstuff, and cosmetics. In this Letter, we present the first quantitative investigation of the flow behavior of single SMLVs in a shearing parallel plate apparatus. We found that SMLVs are deformed and oriented by the action of shear flow while keeping constant volume and exhibit complex dynamic modes (i.e., tumbling, breathing, and tank treading). This behavior can be explained in terms of an excess area (as compared to a sphere of the same volume) and of microstructural defects, which were observed by 3D shape reconstruction through confocal microscopy. Furthermore, the deformation and orientation of SMLVs scale with radius R in analogy with emulsion droplets and elastic capsules (instead of R3, such as in unilamellar vesicles). A possible application of the physical insight provided by this Letter is in the rationale design of processing methods of surfactant-based systems

High-frequency linear rheology of hydrogels probed by ultrasound-driven microbubble dynamics

Ultrasound-driven microbubble dynamics are central to biomedical applications, from diagnostic imaging to drug delivery and therapy. In therapeutic applications, the bubbles are typically embedded in tissue, and their dynamics are strongly affected by the viscoelastic properties of the soft solid medium. While the behaviour of bubbles in Newtonian fluids is well characterised, a fundamental understanding of the effect on ultrasound-driven bubble dynamics of a soft viscoelastic medium is still being developed. We characterised the resonant behaviour in ultrasound of isolated microbubbles embedded in agarose gels, commonly used as tissue-mimicking phantoms. Gels with different viscoelastic properties were obtained by tuning agarose concentration, and were characterised by standard rheological tests. Isolated bubbles (100–200 μm) were excited by ultrasound (10–50 kHz) at small pressure amplitudes (<1 kPa), to ensure that the deformation of the material and the bubble dynamics remained in the linear regime. The radial dynamics of the bubbles were recorded by high-speed video microscopy. Resonance curves were measured experimentally and fitted to a model combining the Rayleigh–Plesset equation governing bubble dynamics, with the Kelvin–Voigt model for the viscoelastic medium. The resonance frequency of the bubbles was found to increase with increasing shear modulus of the medium, with implications for optimisation of imaging and therapeutic ultrasound protocols. In addition, the viscoelastic properties inferred from ultrasound-driven bubble dynamics differ significantly from those measured at low frequency with the rheometer. Hence, rheological characterisation of biomaterials for medical ultrasound applications requires particular attention to the strain rate applied