With the help of a modified atomic force microscope, researchers at the University of California at Berkeley and Stanford University have discovered how the scaffolding matrix of actin within our cells helps them to deal with physical obstacles, allowing cells to propagate, metastasize, and perform such functions as phagocytosis.
From the National Science Foundation website:
To track the growth rate and force generated by actin, the bioengineers modified an atomic force microscope (AFM).
In most research, the business end of an AFM is a miniscule, extremely sharp tip that is attached to a thin silicon-nitride cantilever. Because the tip is so slight, even features as tiny as individual atoms can cause the cantilever to deflect as it passes along, or slightly above, a surface. A laser bounces off the cantilever and into a detector, registering the tiny deflections and providing signals a computer translates into an image.
For this study, the researchers created a specialized AFM that uses two cantilevers and two lasers. Instead of scanning a surface, the cantilevers served as tiny springboards, one to bend as actin grew beneath it and the other to stay as a reference point close to the floor of the sample chamber. Using the two-cantilever system, the researchers pushed longer on the filaments than in any earlier study, and with more force — in some cases to the point where the filaments stalled and could grow no further.
In multiple experiments, the cantilevers applied an initial force to a slurry of growing actin filaments, then applied a larger force for as long as 30 minutes. They then returned to the original load, at every stage tracking how fast the network grew.
Each time, when the cantilever returned to its original load, the growth velocity of the actin was faster. When the fibers endured multiple load cycles, they grew at a rate that was dependent upon all of the cycles.
“We’ve found that the growth of actin is dependent on its loading history — not just on the load it feels at one moment, as we previously thought,” says Fletcher. “This means the structure of a cell has some ‘memory’ of its physical interactions.”
The researchers suspect the effect may relate to filament density, and the growth rate may be a function of the network architecture, itself dependent upon the entire load history.
“For a given load, proteins assume a certain network architecture,” says Fletcher. “This architecture then remodels under a new load. So, if you go back to the original load, the architecture is still tuned for a higher load, resulting in explosive growth.”