We present an in-situ atomic force microscopy (AFM) study of spherical
lipid membranes (also known as liposomes) on a substrate under liquid
. The in-situ AFM observation has been carried out using a commerciall
y available AFM instrument equipped with a fluid cell in the contact m
ode. An immunochemical technique was used to prepare the sample. The A
FM imaging of the liposomes showed their balloon-like structures with
apparent diameters of approximately 200-300 nm. These diameters are es
sentially in agreement with a mean size of 180 nm deduced from a previ
ous dynamic light-scattering experiment, taking account of the well-kn
own broadening phenomenon of lateral sizes in AFM images due to the ti
p-sample convolution. It is shown that the quality (contrast and/or re
producibility) of the AFM images depends both on the types of cantilev
er tips used and on the load forces at which the AFM tips were scanned
over the sample. Based upon this, it is concluded that there is a cer
tain critical contact pressure of a probe tip over the sample, which d
etermines the quality of the sample image taken under water.