Force spectroscopy of cell adhesion molecules

Abstract

Cellular adhesion molecules are placed under force during the highly specific mechanical interactions that occur between proteins of the cell surface and extracellular matrix. In the authors' laboratory they have developed atomic force microscopy (AFM) techniques to study the elastic properties of the extracellular matrix proteins at the single molecule level. The authors demonstrate that extracellular matrix proteins are elastic and that this elasticity involves reversible unfolding of single protein domains. Their data suggest that domain unfolding/refolding could be an important determinant of elasticity in extracellular matrix proteins and that the elastic properties of proteins could play role in cell-cell interactions. Furthermore, the authors have used protein engineering to construct tandem repeats of a single protein module and stretch it with the AFM. This strategy has allowed them to directly measure the unfolding and refolding rates of a single protein domain. They have compared these rates with chemical folding rates for untethered modules and found that the unfolding rates obtained by the two methods are the same. The authors' results demonstrate AFM as a unique tool to study the folding reactions of single protein domains and examine in unprecedented detail the molecular basis of protein elasticity.