The analysis of the vesicle size against time shows a progressive shrinkage, which suggests that the adhesion of SNPs-18@BSA to the GUVs induces a slow gradual rearrangement of the membrane. At the end of the process, the apparent radius of the vesicles is between 30% and 70% smaller compared to the radius of the initial GUV. Note that the decrease in apparent radius is a combination of a genuine decrease in vesicle radius and a drift in the focal plane through the spherical GUV as it shrinks. Threedimensional z-projections indicate that the GUVs exposed to SNPs-18@BSA retain an approximately spherical shape and do not fully collapse (Fig ). From the analysis of 14 GUVs, the average shrinking rate of the vesicle surface area was 4.4 ± 4.9 µm 2 /s. Most of the GUVs observed show an apparent shrinking rate that varies between 1.2 µm 2 /s and 5.8 µm 2 /s, but two isolated events show significantly faster (10.8 µm 2 /s and 18.8 µm 2 /s) shrinking rate (Fig 1c). The variability in shrinking rate likely arises from a combination of variable membrane tension that resists the membrane wrapping the NPs and the rate of stochastic nanoscale pore formation to allow rapid water transport for the GUV to reduce its volume.