Description
The mechanical properties of lipid membranes play an important role in diverse processes, ranging from cellular processes like endocytosis and cytokinesis to cell-cell interactions as well as for diseases like cancer or blood disorders and vesicle based drug delivery systems. Established techniques to probe these mechanics, like micropipette aspiration or optical tweezers however, typically suffer from low throughput. Alternatively, bulk methods like rheometry or scattering techniques primarily provide ensemble-averaged mechanical readouts, such as overall stiffness. These limitations make it challenging to obtain statistically robust measurements of membrane mechanics with a single vesicle resolution.
Here, we introduce a microfluidic platform designed to overcome these limitations, by incorporating hundreds of micropipette like confinements on a single chip. This design enables parallel trapping followed by mechanical characterization of giant unilamellar vesicles (GUVs) in a single experiment. This strategy significantly increases the throughput compared to the sequential testing of one vesicle at a time in conventional techniques. The forces acting on the membrane can be precisely tuned via the applied flow rates, which press the vesicle against the constriction. To quantify the flow, single particle tracking as well as particle image velocimetry was used on tracer particles. Furthermore, the custom geometries of the constrictions, allow for well-defined, controllable mechanical testing. The platform also enables in situ exposure of GUVs to membrane-active compounds, such as surfactants or organic particles, facilitating direct observation of their impact on membrane mechanics. Switching the external medium multiple times between buffer and the substance of interest can be used to probe the dynamic uptake coupled to the resulting change of the mechanics, which further allows to quantify the reversibility of these effects.
This high-throughput approach allows the measurement of membrane mechanics and detects the dynamic response towards compounds of interest. Our platform opens the possibility for systematic screening of libraries, providing a quantitative framework to study the interactions between solutes and their impact on membranes.