Abstract: The familiar biconcave shape of the red-blood cell (RBC) deforms as the cell travels through capillaries. Its dimpled configurations are unique cell shapes and display malleability to form echinocytes, discocytes and stomatocytes, in response to external perturbations. Sheetz and Singer introduced intercalating species to the exterior lipid leaflet of the membrane to promote cup-shaped stomatocytes, and observed that additives to the interior had the opposite effect. Shape transformations appear to be controlled via the RBC bilayer and the asymmetric surface areas of the two leaflets [Proc. Natl. Acad. Sci. U.S.A. 1974, 71, 4457]. Our system promotes area-difference between the lipid bilayer leaflets from a fully symmetrical system and has mimicked the RBC discoid. In our analysis, we explore the system energetic and geometric confinements, which points to transient pores as enablers for the vesicles to deflate and thereby to assume lower profiles.