\end{center}
\end{figure}
-What drives the initial folding? \citet{levinthal68} proposed
-a model based on secondary structure nucleation, but recent work has
-focused on early hydrophobic collapse\citep{TODO}.
-
% why AFM & what an AFM is
-Single molecule techniques for the study of biological macromolecules
-include optical measurements, \ie, single molecule fluorescence
-microscopy and spectroscopy, and mechanical manipulations of
-individual macromolecules, \ie, force microscopy and spectroscopy
+Single molecule techniques provide an opportunity to study protein
+folding and unfolding at the level of a single molecule, where the
+distinction between the pathway model and funnel model is clearer.
+These techniques include optical measurements, \ie, single molecule
+fluorescence microscopy and spectroscopy, and mechanical manipulations
+of individual macromolecules, \ie, force microscopy and spectroscopy
using atomic force microscopes (AFMs), laser tweezers\citep{forde02},
magnetic tweezers\citep{smith92}, biomembrane force
probes\citep{merkel99}, and centrifugal
cantilever is known\citep{levy02}, the force applied to the sample can
be calculated.
-
The forces that can be applied and measured with an AFM range from
tens of piconewtons to hundreds of nanonewtons. The investigation of
the unfolding and refolding processes of individual protein molecules