**DNA, Chromatin and Membranes**

174 Atomic Force Microscopy Investigations into Biology – From Cell to Protein

Toyama, B. H., & Weissman, J. S. (2011). Amyloid Structure: Conformational Diversity and

Tsigelny, I. F., Bar-On, P., Sharikov, Y., Crews, L., Hashimoto, M., Miller, M. A., et al. (2007).

Tskhovrebova, L., Trinick, J., Sleep, J. A., & Simmons, R. M. (1997). Elasticity and unfolding of single molecules of the giant muscle protein titin. *Nature, 387* (6630), 308-312. VanLandingham, M. R., Juliano, T. F., & Hagon, M. J. (2005). Measuring tip shape for

Vollrath, F., & Knight, D. P. (2001). Liquid crystalline spinning of spider silk. *Nature, 410*

Wasmer, C., Lange, A., Van Melckebeke, H., Siemer, A. B., Riek, R., & Meier, B. H. (2008).

Weisenhorn, A. L., Hansma, P. K., Albrecht, T. R., & Quate, C. F. (1989). Forces in Atomic Force Microscopy in Air and Water. *Applied Physics Letters, 54* (26), 2651-2653. Westermark, G. T., Johnson, K. H., & Westermark, P. (1999). [1] Staining methods for

Yu, J., Malkova, S., & Lyubchenko, Y. L. (2008). α-Synuclein Misfolding: Single Molecule AFM Force Spectroscopy Study. *Journal of Molecular Biology, 384* (4), 992-1001. Zenhausern, F., Adrian, M., Tenheggelerbordier, B., Eng, L. M., & Descouts, P. (1992). DNA

Influence of Molecular-Scale Friction. *Scanning, 14* (4), 212-217.

(Eds.), *Annual Review of Biochemistry, Vol 80* (Vol. 80, pp. 557-585).

development by beta-synuclein. *Febs Journal, 274* (7), 1862-1877.

*Technology, 16* (11), 2173-2185.

hydrophobic core. *Science, 319* (5869), 1523-1526.

Volume 309, pp. 3-25): Academic Press.

(6828), 541-548.

Consequences. In R. D. Kornberg, C. R. H. Raetz, J. E. Rothman & J. W. Thorner

Dynamics of alpha-synuclein aggregation and inhibition of pore-like oligomer

instrumented indentation using atomic force microscopy. *Measurement Science &* 

Amyloid fibrils of the HET-s (218-289) prion form a beta solenoid with a triangular

identification of amyloid in tissue. In W. Ronald (Ed.), *Methods in Enzymology* (Vol.

and Rna-Polymerase DNA Complex Imaged by Scanning Force Microscopy -

**8** 

**Analyzing DNA Structure Quantitatively** 

*School of Chemistry and Chemical Engineering, Southeast University, Nanjing* 

The atomic force microscope (AFM), one of the most popular types of scanning probe microscopy, was invented by Binnig *et al* 1 in 1986. After that, its quick development resulted in the commercial AFM available at 1989 to the biological and chemical researchers. Two decades after its invention, now it has become a standard measurement technique in multiple branches of science and technology. The AFM's advantage over other techniques stems from its ability to work in different environment. It can work in vacuum, liquid, or ambient, and in addition its high resolution and sensitivity to measure spatial sizes and forces, respectively. The technique thus not only provides sharp images of nonconductive surfaces at a resolution of nanometer scale, but also enables the measurements of intra- or inter-molecular forces at a resolution of pico-newton scale. These properties make AFM

The schematic in Figure 1A illustrates the basic principles of the AFM operation. A sharp tip reads the profile of the sample by scanning the surface. The tip is attached to a cantilever that works as a spring pressing the tip against the sample. The vertical position of the tip is measured by a laser reflected from the cantilever to the position of sensitive photo detector (PSPD). Three important features of the AFM instrument are listed below. First, the position of the sample relative to the tip is controlled by the scanner and it can be done with accuracy better than 1 nm. Second, the tip may be made tremendously sharp or customized for the desired measurement. Third, the vertical displacement of the tip relative to the surface is determined with sub-nanometer precision. These three major features allow AFM to provide

Figure 1B illustrates the major operation modes of the AFM. The manner of the microscope operation corresponding to the attraction part of the tip-sample interaction potential is noncontact mode (NC-AFM) 3. A breakthrough in the high-resolution AFM imaging was made with implementation of the NC-AFM mode, offering a unique tool for real space atomicscale studies of surfaces and nanoparticles. The probe of NC mode does not contact the sample surface, but oscillates above the adsorbed fluid layer on the surface during scanning. Using a feedback loop to monitor changes in the amplitude due to attractive forces the surface topography can be measured. After tip-surface attraction force passes the minimum

ideal for biological samples, especially for DNA molecules.

the topographic image with nanometer resolution.

**1. Introduction** 

**at a Single-Molecule Level by** 

**Atomic Force Microscopy** 

Yong Jiang and Yuan Yin

*P. R. China* 
