The membrane surface of polarized renal epithelial cells (MDCK cells)
grown as a monolayer was imaged with the atomic force microscope. The
surface topography of dried cells determined by this approach was cons
istent with electron microscopy images previously reported. Fixed and
living cells in aqueous medium gave more fuzzy images, likely because
of the presence of the cell glycocalix. Treatment of living cells with
neuraminidase, an enzyme that partly degrades the glycocalix, allowed
sub-micrometer imaging. Protruding particles, 10 to 60 nm xy size, oc
cupy most of the membrane surface. Protease treatment markedly reduced
the size of these particles, indicating that they corresponded to pro
teins. Tip structure effects were probably involved in the exaggerated
size of imaged membrane proteins. Although further improvements in th
e imaging conditions, including tip sharpness, are required, atomic fo
rce microscope already offers the unique possibility to image proteins
at the membrane surface of living cells.