Mechanical performance of hybrid polymer-lipid vesicles with leaflet asymmetry engineered using microfluidics

Lipid vesicles consist of aqueous cores surrounded by a bilayer of phospholipids. Hybrid polymer-lipid vesicles incorporate both polymers and lipids, offering promising properties for developing pharmaceuticals, biosensors, and artificial cells. The hybrid vesicles can be symmetric, in which their two leaflets contain identical compositions, or asymmetric, in which the leaflets possess dissimilar compositions and can lead to dramatically modified properties. However, methods to produce both symmetric and asymmetric hybrid vesicles result in heterogenous compositions and sizes, making it challenging to quantify the effect of asymmetry and limiting applications. Here, we use a microfluidic approach to produce hybrid vesicles containing symmetric or asymmetric leaflets with precisely engineered compositions. We find the vesicles with asymmetric leaflets are significantly stiffer and tougher than those with symmetric leaflets; moreover, the lateral diffusivity of lipids is greatly decreased. The optimum structure consists of an inner leaflet that is a stretchable lipid leaflet and an outer leaflet that is a fully continuous polymer leaflet. This technique of precisely engineering asymmetric structures can be applied to hybrid vesicles composed of other types of polymers and lipids, further expanding their potential applications.