Abstract

Vesicle 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.

Highlights

  • With respect to the mechanical properties of the membrane

  • Since the membrane composition varies significantly between different cell types and between organelles within a cell[28], and can be altered by diseases[29], mechanical selectivity of vesicle rupture would open up the potential for new sorting methods

  • We tuned the mechanical properties of giant unilamellar vesicles by tuning the lipid composition of the membrane using different lipids (SOPC, DOPC, POPC) and lipid:cholesterol mixtures (SOPC:chol, DOPC:chol)

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Summary

Results and Discussion

We observed the deformation and rupture of vesicles in the acoustic microstreaming flow generated by an ultrasound-driven microbubble oscillating near a solid wall (see Fig. 1). The radial oscillations of the bubble near a rigid wall, with amplitude ε′a, where a ≈ 10–100 μm is the bubble radius, result in translational oscillations of the center of mass, with amplitude εa[30]. We measured the maximum strain rate from experimental streamlines for spherical oscillations, and compared the experimental values with the results of Equation (1) (see Fig. 1f). The model for vesicle deformation introduced in Ref. 18, which takes into account stretching of the membrane, predicts a threshold value of the capillary number for vesicle rupture: D

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DOPC:chol rupture no rupture
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