Whether mechanically unfolded fibronectin (Fn) is present within native extracellular matrix fibrils is controversial. Fn extensibility under the influence of cell traction forces has been proposed to originate either from the force-induced lengthening of an initially compact, folded quaternary structure as is found in solution (quaternary structure model, where the dimeric arms of Fn cross each other), or from the force-induced unfolding of type III modules (unfolding model). Clarification of this issue is central to our understanding of the structural arrangement of Fn within fibrils, the mechanism of fibrillogenesis, and whether cryptic sites, which are exposed by partial protein unfolding, can be exposed by cell-derived force. In order to differentiate between these two models, two fluorescence resonance energy transfer schemes to label plasma Fn were applied, with sensitivity to either compact-to-extended conformation (arm separation) without loss of secondary structure or compact-to-unfolded conformation. Fluorescence resonance energy transfer studies revealed that a significant fraction of fibrillar Fn within a three-dimensional human fibroblast matrix is partially unfolded. Complete relaxation of Fn fibrils led to a refolding of Fn. The compactly folded quaternary structure with crossed Fn arms, however, was never detected within extracellular matrix fibrils. We conclude that the resting state of Fn fibrils does not contain Fn molecules with crossed-over arms, and that the several-fold extensibility of Fn fibrils involves the unfolding of type III modules. This could imply that Fn might play a significant role in mechanotransduction processes.

Tribology is the study of adhesion, friction, lubrication and wear of surfaces in relative motion. It remains as important today as it was in ancient times, arising in the fields of physics, chemistry, geology, biology and engineering. The more we learn about tribology the more complex it appears. Nevertheless, recent experiments coupled to theoretical modelling have made great advances in unifying apparently diverse phenomena and revealed many subtle and often non-intuitive aspects of matter in motion, which stem from the nonlinear nature of the problem.

We review the historical and modern understanding of the most basic equation of friction, Amontons' law, which describes phenomena that were already understood and studied by Leonardo da Vinci 500 years ago. This law states that for any two materials the (lateral) friction force is directly proportional to the (normal) applied load, with a constant of proportionality, the friction coefficient, that is constant and independent of the contact area, the surface roughness, and the sliding velocity. No theory has yet satisfactorily explained this surprisingly general law; all attempts have been model or system dependent. We review the experimental evidence and find, for example, that the same friction coefficient is often measured for the same system of materials with junctions whose areas differ by more than 6 orders of magnitude. The trends obtained through molecular dynamics (MD) simulations agree with recent and past experiments and with Amontons' law, and they suggest that the local energy-dissipating mechanisms are not merely "mechanical", as assumed in most models, but "thermodynamic" in nature, like miniature irreversible compression-decompression cycles of the trapped molecules between the surface asperities as they pass over each other. The MD analysis reveals that, for such dynamic, nonequilibrium, energy-dissipating processes, a proper statistical description can be formulated through the use of the Weibull distribution of the local friction forces, which may be regarded to serve in this context a similar purpose as the Boltzmann distribution for classical systems at equilibrium. Another important conclusion is that the concept of the "real" area of contact is a nonfundamental quantity, whether at the nano-, micro-, or macroscale. However, it may serve as a convenient scaling parameter for describing the really fundamental parameters, which are the number density of atoms, molecules, or bonds involved in an adhesive or frictional interaction. Brief History of the Concept of the "Coefficient of Friction"