Microfluidic characterization of biomimetic membrane mechanics with an on-chip micropipette

The mechanic properties of cell membranes control many biological processes. The complexity of natural membranes is often dealt with by building synthetic vesicles (Giant Unilamellar Vesicles, GUVs), which can be thought as micron-sized minimal cells. Micropipette aspiration technique is the gold standard to characterize membrane mechanics, but it involves manual, long and tedious experiments. Microfluidics is perfectly suited to handle GUVs and permits in particular to conceive on-chip micropipettes for automated, systematic studies of membrane mechanical moduli. We developed a microfabrication process that enables obtaining the required 3-level channels including a micropipette in the intermediate level, with micrometric alignment, sufficiently low adhesion and roughness. We extended the theoretical analysis of micropipette, valid for cylindrical geometries that microfabrication does not allow, to the on-chip geometry, by considering the deformation of a vesicle in a square cross-section trap. We confirmed the validity of our approach thanks to systematic experiments performed on GUVs with well-characterized compositions: the obtained values of the membrane stretching modulus are in quantitative agreement with the literature. As a case study, we used our device to show that GUVs challenged with copolymer micelles, typically used for drug delivery, displayed a significantly decrease of the membrane stretching modulus, which could mediate internalization of these nanovectors. This study opens the path to systematic studies of the influence of physico-chemical environment on the mechanics of cell membranes.