The effect of various drugs affecting the integrity of different components of the cytoskeleton on the elasticity of two fibroblast cell lines was investigated by elasticity measurements with an atomic force microscope (AFM). Disaggregation of actin filaments always resulted in a distinct decrease in the cell's average elastic modulus indicating the crucial importance of the actin network for the mechanical stability of living cells. Disruption or chemical stabilization of microtubules did not affect cell elasticity. For the f-actin-disrupting drugs different mechanisms of drug action were observed. Cytochalasins B and D and Latrunculin A disassembled stress fibers. For Cytochalasin D this was accompanied by an aggregation of actin within the cytosol. Jasplakinolide disaggregated actin filaments but did not disassemble stress fibers. Fibrous structures found in AFM images and elasticity maps of fibroblasts could be identified as stress fibers by correlation of AFM data and fluorescence images.

We have measured force curves as a function of the lateral position on top of human platelets with the atomic force microscope. These force curves show the indentation of the cell as the tip loads the sample. By analyzing these force curves we were able to determine the elastic modulus of the platelet with a lateral resolution of approximately 100 nm. The elastic moduli were in a range of 1-50 kPa measured in the frequency range of 1-50 Hz. Loading forces could be controlled with a resolution of 80 pN and indentations of the platelet could be determined with a resolution of 20 nm.

Since its invention a few years ago, the atomic force microscope has become one of the most widely used near-field microscopes. Surfaces of hard sample are imaged routinely with atomic resolution. Soft samples, however, remain challenging. An overview is presented on the application of atomic force microscopy to organic samples ranging from thin ordered films at molecular resolution to living cells. Fundamental mechanisms of the image formation are discussed, and novel imaging modes are introduced that exploit different aspects of the tip-sample interaction for local measurements of the micromechanical properties of the sample. As examples, images of Langmuir-Blodgett films, which map the local viscoelasticity as well as the friction coefficient, are presented.

The elastic properties of thin gelatin films were investigated with the atomic force microscope (AFM). The degree of swelling and thus the softness of the gelatin can be tuned by immersing it in mixtures of propanol and water. Therefore, we have chosen gelatin films as a model system to characterize the measurement of elasticity of thin and soft samples. The major aim of this study was to investigate the influence of the film thickness on the apparent elastic (Young's) modulus. Thus, we prepared wedge-shaped samples with a well-defined thickness of up to 1 μm. The Young's modulus of our samples was between 1 MPa and 20 kPa depending on the degree of swelling. The elasticity was calculated by analyzing the recorded force curves with the help of the Hertz model. We show that the calculated Young's modulus is dependent on the local film thickness and the applied loading force of the AFM tip. Thus, the influence of the hard substrate on the calculated softness of the film can be characterized as a function of indentation. It was possible to determine the elastic properties of gelatin films with a thickness down to 50 nm and a Young's modulus of ∼20 kPa.

Tapping mode atomic force microscopy in liquids gives a substantial improvement in imaging quality and stability over standard contact mode. In tapping mode the probe-sample separation is modulated as the probe scans over the sample. This modulation causes the probe to tap on the surface only at the extreme of each modulation cycle and therefore minimizes frictional forces that are present when the probe is constantly in contact with the surface. This imaging mode increases resolution and reduces sample damage on soft samples. For our initial experiments we used a tapping frequency of 17 kHz to image deoxyribonucleic acid plasmids on mica in water. When we imaged the same sample region with the same cantilever, the plasmids appeared 18 nm wide in contact mode and 5 nm in tapping mode.