抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

http://experimentationlab.berkeley.edu/sites/default/files/AFMImages/butt_AFM.pdf

Force measurements with the atomic force microscope: Technique, interpretation and applications

This article reviews the progress of atomic force microscopy in ultrahigh vacuum, starting with its invention and covering most of the recent developments. Today, dynamic force microscopy allows us to image surfaces of conductors and insulators in vacuum with atomic resolution. The most widely used technique for atomic-resolution force microscopy in vacuum is frequency-modulation atomic force microscopy (FM-AFM). This technique, as well as other dynamic methods, is explained in detail in this article. In the last few years many groups have expanded the empirical knowledge and deepened our theoretical understanding of frequency-modulation atomic force microscopy. Consequently spatial resolution and ease of use have been increased dramatically. Vacuum atomic force microscopy opens up new classes of experiments, ranging from imaging of insulators with true atomic resolution to the measurement of forces between individual atoms.

https://hep.physics.utoronto.ca/WilliamTrischuk/courses/phy189/AFM_revmodphys.pdf

Advances in atomic force microscopy

Dynamic atomic force microscopy methods

Fibroblasts can condense a hydrated collagen lattice to a tissue-like structure 1/28th the area of the starting gel in 24 hr. The rate of the process can be regulated by varying the protein content of the lattice, the cell number, or the con- centration of an inhibitor such as Colcemid. Fibroblasts of high population doubling level propagated in vitro, which have left the cell cycle, can carry out the contraction at least as efficiently as cycling cells. The potential uses of the system as an immu- nologically tolerated "tissue" for wound hea ing and as a model for studying fibroblast function are discussed.

Production of a tissue-like structure by contraction of collagen lattices by human fibroblasts of different proliferative

Frequency modulation atomic force microscopy utilizes the change in resonant frequency of a cantilever to detect variations in the interaction force between cantilever tip and sample. While a simple relation exists enabling the frequency shift to be determined for a given force law, the required complementary inverse relation does not exist for arbitrary oscillation amplitudes of the cantilever. In this letter we address this problem and present simple yet accurate formulas that enable the interaction force and energy to be determined directly from the measured frequency shift. These formulas are valid for any oscillation amplitude and interaction force, and are therefore of widespread applicability in frequency modulation dynamic force spectroscopy.

Accurate formulas for interaction force and energy in frequency modulation force spectroscopy

Atomic force microscopes typically require knowledge of the cantilever spring constant and optical lever sensitivity in order to accurately determine the force from the cantilever deflection. In this study, we investigate a technique to calibrate the optical lever sensitivity of rectangular cantilevers that does not require contact to be made with a surface. This noncontact approach utilizes the method of Sader et al. [Rev. Sci. Instrum. 70, 3967 (1999)] to calibrate the spring constant of the cantilever in combination with the equipartition theorem [J. L. Hutter and J. Bechhoefer, Rev. Sci. Instrum. 64, 1868 (1993)] to determine the optical lever sensitivity. A comparison is presented between sensitivity values obtained from conventional static mode force curves and those derived using this noncontact approach for a range of different cantilevers in air and liquid. These measurements indicate that the method offers a quick, alternative approach for the calibration of the optical lever sensitivity.

/pdf/noninvasive-determination-of-optical-lever-sensitivity-in-nwi318984d.pdf

Noninvasive determination of optical lever sensitivity in atomic force microscopy

We have developed a liquid-environment frequency modulation atomic force microscope (FM-AFM) with a low noise deflection sensor for a wide range of cantilevers with different dimensions. A simple yet accurate equation describing the theoretical limit of the optical beam deflection method in air and liquid is presented. Based on the equation, we have designed a low noise deflection sensor. Replaceable microscope objective lenses are utilized for providing a high magnification optical view (resolution: <3μm) as well as for focusing a laser beam (laser spot size: ∼10μm). Even for a broad range of cantilevers with lengths from 35to125μm, the sensor provides deflection noise densities of less than 11fm∕Hz in air and 16fm∕Hz in water. In particular, a cantilever with a length of 50μm gives the minimum deflection noise density of 5.7fm∕Hz in air and 7.3fm∕Hz in water. True atomic resolution of the developed FM-AFM is demonstrated by imaging mica in water.

Development of liquid-environment frequency modulation atomic force microscope with low noise deflection sensor for cantilevers of various dimensions

https://www.cell.com/biophysj/pdf/S0006-3495(07)71162-1.pdf

Direct Imaging of Individual Intrinsic Hydration Layers on Lipid Bilayers at Ångstrom Resolution

Combining a carbon nanotube probe and a highly sensitive dynamic measurement scheme has enabled us to use atomic force microscopy to measure oscillatory forces in water on approaching a surface that has been laterally characterized on a nanometer scale. This opens up the possibility of investigating water layers under a variety of experimental conditions and as a function of precise lateral position on any surface including biological membranes and macromolecules. Among the many and varied roles of water layers are effects on biomolecular adhesion, colloid dispersion, and tribology, which can now be investigated with nanometer lateral resolution and with a wider range of materials than that previously provided by surface forces appartus.

Suzanne P. Jarvis

Papers

Accurate formulas for interaction force and energy in frequency modulation force spectroscopy

Noninvasive determination of optical lever sensitivity in atomic force microscopy

Development of liquid-environment frequency modulation atomic force microscope with low noise deflection sensor for cantilevers of various dimensions

Direct Imaging of Individual Intrinsic Hydration Layers on Lipid Bilayers at Ångstrom Resolution

Local Solvation Shell Measurement in Water Using a Carbon Nanotube Probe