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Atomic force microscopy (AFM) was first used in 1986 and uses a cantilever with a sharp tip to scan across a sample to produce a topographic map. The process is now expanding its use over a range of applications.
AFM is a form of scanning probe microscopy, and it is known to provide nanometer-resolution assessments of biological or other material samples in terms of their height, friction, or magnetism. The microscope generally has a low lateral resolution of ~30 nm, but a high vertical resolution of up to 0.1 nm.
Never Before Seen Chemical Reactions
A new application of AFM is to witness new chemical reactions that are never before seen. A team of chemists and physicists from the University of California, Berkeley, and Lawrence Berkeley National Laboratory used AFM to create snapshots as two known molecules react on the surface of a catalyst. They saw molecules that they would consider chemical intermediates in the chemical reaction that lasted about 20 minutes.
In the near future scientists predict that AFM will provide new insights about chemical reaction rules, allowing chemists to better manipulate them or to build new molecules that were never created before.
AFM For Drug Development
AFM is already taking its place as a tool in drug development. Drugs applied to molecules scanned by AFM have shown on a nanoscale level how a drug has impacted cell membranes, including their elasticity, which is important given that approximately half of approved drugs are those that in some way interact with membrane proteins on a cell’s surface.
AFM also allows for the observation and evaluation of complex molecular dynamics that occur during the association and dissociation processes of individual drug-target interactions. It reveals so much that model simulations do not need to be taken out. Again, traditional methods such as surface plasma resonance or radio immunoassays do not provide such direct morphological information that comes out of real-time responses of a target molecule being affected by a drug.
By 2008 high-speed AFM achieved a feedback bandwidth of ~100 kHz to image protein molecules at sub-100 ms temporal resolution as they acted naturally.
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Nanoscale Assessments of Cells
With such advances, AFM can now obtain multiple nanoscale assessments of aspects of cells such as its morphology, elasticity, adhesion, deformation and energy dissipation in a few minutes. All of these dimensions can be correlated as a response ‘map’ to a drug.
Scientists at Case Western Reserve in Cincinnati, OH have been particularly excited to view how proteins actually behave when they are naturally embedded in a lipid bilayer in a cell. This natural behavior is critical, given how important the membrane proteins’ and lipids’ functions are. The membrane proteins transmit information from outside to inside the cell using bindings ligands to first sense the external environment.
Other methods of studying the proteins, such as the use of fluorescent tags or a staining agent, change the proteins, which alters the behaviors they make. AFM does not require protein labeling of proteins, so they can be assessed within the context of a lipid bilayer and with their native qualities intact. Better and more rapid insights about proteins are thought to lead to faster and more effective drug development.
AFM Improvements
Improvements to AFM will aid scientists in the near future, these improvements include the cantilevers as well as continued refinements in the use of AFM with other techniques, including other microscopy and spectroscopy methods. In this way, all of the methods’ strengths can be leveraged, and perhaps their weaknesses minimized, during even more multidimensional and, ultimately, time-saving examinations.
References and Further Reading
Atomic Force Microscopy
Nanoscale Monitoring of Drug Actions on Cell Membrane Using Atomic Force Microscopy
Fundamental Theory of Atomic Force Microscopy
Atomic Force Microscope Reveals Chemical Ghosts
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