[Force spectroscopy][fs] is the process of extracting information
about the unfolding (or unbinding) characteristics of a protein (or
ligand-receptor pair) by measuring force vs. extension curves while
gradually ripping the protein (or pair) apart.  Consider this cartoon
representation of the procedure

[[!img afm_protein_pulling_cartoon.jpg size="300x"
  alt="Protein unfolding cartoon"
  title="Protein unfolding cartoon"]]

The AFM tip is pulling a protein chain away from the substrate,
causing one of the protein domains to uncoil.

The procedure yields 'force curves' like this

[[!img force_curve_regions.png
  alt="Protein unfolding force curve"
  title="Protein unfolding force curve"]]

To interpret the force curve, let us examine it piece-by-piece as the
AFM tip gradually pulls away from the substrate.

1. The linear 'contact' region demonstrates the Hooke's law behavior
   of the AFM cantilever, with force ∝ displacement.
2. The high force 'bulge' linking the contact region to the sawtooth
   comes from the AFM tip pulling free of the surface and associated
   protein 'mat' (the cartoon being excessively pretty, and our sample
   having too high a protein concentration :p).
3. The characteristic 'sawtooth' comes from several identical domains
   unfolding one after the other.
4. After the last of the protein domains unfolds the protein snaps off
   of the AFM tip (or the substrate), and the deflection of the
   now-free cantilever ceases to depend on distance.

[[!img force_curve_regions_cantilever.png
  alt="Force curve cantilever positions"
  title="Force curve cantilever positions"]]

[fs]: http://en.wikipedia.org/wiki/Force_spectroscopy

[[!tag tags/theory]]