From Shallow to Full Wrapping: Geometry and Deformability Dictate Lipid Vesicle Internalization.

The deformability and adhesion of vesicles critically influence their engulfment by lipid membranes, a process that is central to endocytosis, viral entry, drug delivery, and intercellular transport. We developed a versatile experimental system of giant unilamellar vesicles (GUVs) that interact via depletion-induced adhesion. Combining experiments with continuum simulations, we construct a state diagram identifying conditions for the endo- and exocytic engulfment of small GUVs by larger ones. Leveraging full 3D confocal reconstructions of vesicle curvature, we experimentally quantify the bendocapillary length, a scale governing the competition between membrane bending and adhesion. When the vesicle size exceeds this length, wrapping is governed by geometry. In contrast, near this scale, deformability controls transitions between shallow, deep, and fully wrapped states, suppressing full engulfment. Finally, we demonstrate on-demand, light-induced switching between wrapping states using photoresponsive lipids. These results establish a mechanical criterion for vesicle engulfment and provide a tunable platform for studying soft cargo uptake.