A number of elaborate adhesion systems and theories based on fluid phospholipid membranes have been investigated, but most of this research has been limited to homogeneous situations of similar size vesicles, such as LUV/LUV (Large Unilamellar Vesicles) or GUV/GUV (Giant Unilamellar Vesicles). In this study, we focus on heterogeneous adhesion between two different sized phospholipid vesicles (GUV/ LUV) functionalized with two specific adhesion systems; these are the irreversible biotin-avidin interaction and reversible DNA hybridization. We explore programming hierarchical structures and their unique morphology driven by adhesion between GUVs and LUVs via these two, simultaneous binding methods. A GUV, about 10 µm in diameter, acts as a template for LUVs (approximately 100 nm in diameter) to bind onto the GUV membrane surface via complementary DNA hybridization. LUVs are then irreversibly cross-linked (“bio-welded”) via avidin-biotin binding, the kinetics of which depends upon the tether length of the biotin-functionalized lipid. Phase-contrast microscopy images and quantitative measurements of fluorescence intensities at the adhesive interface confirm GUV/LUV adhesion and the production of cross-linked hollow vesicle superstructures. Micropipette aspiration is used to characterize the different mechanical properties of the GUV/LUVs superstructures compared to unmodified GUVs: cross-linking of LUVs on the GUV surface significantly increases the elastic modulus and critical lysis tension of the system. Finally, a dual micropipettes aspiration technique demonstrates contact angles which are related to the adhesion strength between vesicle membranes for the two binding techniques.