Unravelling the design principles for single protein mechanical strength.

In recent years single molecule manipulation techniques have improved to the extent that measurements of the mechanical strength of single proteins can now be undertaken routinely. This powerful new tool, coupled with theoretical frameworks to characterise the unfolding process, has enabled significant progress to be made in understanding the physical mechanisms that underlie protein mechanical strength. These design concepts have allowed the search for proteins with novel, mechanically strong folds to be automated and for previously mechanically characterised proteins to be engineered rationally. Methods to achieve the latter are diverse and include re-engineering of specific hydrophobic core residues, changing solvent conditions and the 'cross-linking' of side-chains that are separated in the rate-limiting unfolding transition. Predicting the mechanical behaviour of larger proteins and those with more complex structures remains a significant challenge while on-going instrument development is beginning to allow the examination of mechanical strength of protein across a wide range of force loading rates. The integral role of force in biology and the potential for exploitation of catalytic and structural proteins as functional bio-materials makes this a particularly important area of research. Copyright (c) 2010 Elsevier Ltd. All rights reserved.