Publisher Summary This chapter explores the dynamic topography change of PC and PE liposomes from a vesicle form to a flat bilayer through their direct adhesion on a mica surface by Atomic Force Microscope in situ. In the PC liposome, the second bilayer was hardly formed and only a saturated first bilayer is extended over the all mica surface. On the other hand, in PE liposome system, a vertical growth of lipid molecules was recognized. This different behavior is interpreted by the existence of hydration layer around the PC surface. As a solid substrate, a moscovite mica is chosen and used immediately after cleavage in a clean atmosphere. Two kinds of phospholipid, phosphatidylcholine (PC) from egg yolk and phosphatidylethanolamine (PE) from bovine brain, are used without further purification. The electrostatic interaction between PC liposome and mica surface is an important factor in determining the adhesion rate. Furthermore, it is realized that even though succesive scanning for the exposed area by using the same high force and the same high speed, a further deep defect could not be created on any defect surfaces. The results indicate that the adhesion of PE head groups on mica is more strong than the adhesion between PE head groups themselves and a some interaction force between the phospholipid membranes, probably a hydration force (layer) on their surfaces, influence on the deformation process of PE vesicles on mica surface.This chapter also shed light on the adhesion process of PC and PE liposomes on a mica surface has been observed in situ by the AFM to understand the deformation mechanism from the vesicle form to the flat bilayer.