Force Spectroscopy Experiments
How proteins fold into fully functional 3D structures remains one of the most researched areas in biology and medicine. It is also a complex challenge faced by every living cell. Indeed, when proteins misfold as a result of mutations or external factors, countless diseases are known to occur, such as Alzheimer's, Mad Cow and Parkinson's disease. Unless the cell degrades those proteins sufficiently fast, they are known to aggregate and may even cause cell death.
While much is known about crystallized protein structures, experimental tools that can probe the conformations exhibited by the protein along its folding pathway have only recently emerged. Most such experiments are performed in the bulk, averaging over a huge ensemble of molecules and smearing out the details of the process. The underlying principles that ensure correctly folded structures are therefore best examined at the single molecule level.
Using the recently developed force-clamp spectroscopy (figure 1), we apply force to a single protein (figure 2), which is a process that is present in nature, most obviously in the case of muscle proteins. These mechanically stable proteins exhibit interesting unfolding and refolding properties under force [1,2], which reveal their complex kinetics and a multiplicity in their folding pathways. We use statistical physics tools to understand the signatures of complexity from the measured folding and unfolding trajectories.