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Guanine, one ofthe four DNA bases, has been observed by tunneling microscopy to form a two-dimensional ordered structure on two crystalline substrates, graphite and MoS2. The two-dimensional lattice formed by guanine is nearly identical on the two surfaces, and heteroepitaxy appears to be the growth mechanism in both cases. Although the resolution of molecular details is superior for the graphite substrate, the simpler results on MoS2 are not only easier to interpret but also facilitate the understanding of the more complex images on graphite. We propose that the interfacial structure is composed of linear chains of hydrogen-bonded molecules aligned into a closely packed two-dimensional array.Several recent studies have examined the possibility of imaging DNA by scanning tunneling microscopy (STM) (1-3). However, the ultimate goal-to read the code contained in the strands-has not yet been achieved. To do so it must be possible to recognize clearly and distinguish between the four bases of the genetic code. One essential requirement for imaging small organic molecules by STM is to find experimental preparation conditions whereby the molecules stick firmly to the substrate and form a highly stable layer. This is necessary to withstand the forces of the STM tip during imaging. Compared to the binding of complete DNA strands to the basal planes of MoS2 or graphite, the adsorption of "naked" nucleotide bases is favored by their greater hydrophobicity and, as is shown in this report, by their ability to register with the substrate, thus forming a stable twodimensional ordered array. No signs of mobility were observed during investigations, which lasted up to 1 h in a single region. That such an array can form is probably due to the intermolecular hydrogen bonding capability of the DNA bases (4).Ordered molecular layers of organic molecules, such as benzene (5), alkanes (6), or liquid crystals (7,8), are the most prominent examples to have been imaged recently by STM at atomic resolution. STM results of adenine, one of the four DNA bases, have recently been obtained on graphite by Allen et al. (9). Using a sample preparation technique similar to theirs (9), we prepared samples of guanine on the surfaces of natural MoS2 crystals and highly oriented pyrolytic graphite. We often observed steps from the bare substrate to monolayers of guanine. The results presented in this paper were obtained on such monolayer islands. The character of the steplines provides additional information since the orientation of the molecular lattice with respect to the substrate can be measured there. In the STM images the bases look quite different depending on whether they are deposited on MoS2 (Fig. 1) or on graphite (see Fig. 3). The main differences are that on MoS2 the bases appear as distinct well-isolated nearly structureless blobs; on graphite more details become visible, although it is still not possible to determine the 8003The publication costs of this article were defrayed in part by page charge payment. This article must ...

By means of scanning tunneling microscopy, it is observed that molecules of the form n-alkylcyanobiphenyl, where n = 8 to 12, form two-dimensional crystalline domains when adsorbed onto graphite. The layer spacings measured by tunneling microscopy are 20% larger than those measured previously on bulk material by x-ray diffraction. The structure of the adsorbed molecules is quite different from that of the bulk.

Single living cells were studied in growth medium by atomic force microscopy at a high--down to one image frame per second--imaging rate over time periods of many hours, stably producing hundreds of consecutive scans with a lateral resolution of approximately 30-40 nm. The cell was held by a micropipette mounted onto the scanner-piezo as shown in Häberle, W., J. K. H. Hörber, and G. Binnig. 1991. Force microscopy on living cells. J. Vac. Sci. Technol. B9:1210-0000. To initiate specific processes on the cell surface the cells had been infected with pox viruses as reported earlier and, most likely, the liberation of a progeny virion by the still-living cell was observed, hence confirming and supporting earlier results (Häberle, W., J. K. H. Hörber, F. Ohnesorge, D. P. E. Smith, and G. Binnig. 1992. In situ investigations of single living cells infected by viruses. Ultramicroscopy. 42-44:1161-0000; Hörber, J. K. H., W. Häberle, F. Ohnesorge, G. Binnig, H. G. Liebich, C. P. Czerny, H. Mahnel, and A. Mayr. 1992. Investigation of living cells in the nanometer regime with the atomic force microscope. Scanning Microscopy. 6:919-930). Furthermore, the pox viruses used were characterized separately by AFM in an aqueous environment down to the molecular level. Quasi-ordered structural details were resolved on a scale of a few nm where, however, image distortions and artifacts due to multiple tip effects are probably involved--just as in very high resolution (<15-20 nm) images on the cells. Although in a very preliminary manner, initial studies on the mechanical resonance properties of a single living (noninfected) cell, held by the micropipette, have been performed. In particular, frequency response spectra were recorded that indicate elastic properties and enough stiffness of these cells to make the demonstrated rapid scanning of the imaging tip plausible. Measurements of this kind, especially if they can be proven to be cell-type specific, may perhaps have a large potential for biomedical applications. Images of these living cells were also recorded in the widely known (e.g., Radmacher, M., R. W. Tillmann, and H. E. Gaub. 1993. Imaging viscoelasticity by force modulation with the atomic force microscope. Biophys. J. 64:735-742) force modulation mode, yet at one low modulation frequency of approximately 2 kHz. (Note: After the cells were attached to the pipette by suction, they first deformed significantly and then reassumed their original spherical shape, which they also acquire when freely suspended in solution, to a great extent with the exception of the portion adjusting to the pipette edge geometry after approximately 0.5-1 h, which occurred in almost the same manner with uninfected cells, and those that had been infected several hours earlier. This seems to be a process which is at least actively supported by the cellular cytoskeleton, rather than a mere osmotic pressure effect induced by electrolyte transport through the membrane. Furthermore, several hours postinfection (p.i.) infected cells developed many opticall...

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