Rather than maximizing toughness, as needed for silk and muscle titin fibers to withstand external impact, the much softer extracellular matrix fibers made from fibronectin (Fn) can be stretched by cell generated forces and display extraordinary extensibility. We show that Fn fibers can be extended more than 8-fold (>700% strain) before 50% of the fibers break. The Young's modulus of single fibers, given by the highly nonlinear slope of the stressstrain curve, changes orders of magnitude, up to MPa. Although many other materials plastically deform before they rupture, evidence is provided that the reversible breakage of force-bearing backbone hydrogen bonds enables the large strain. When tension is released, the nano-sized Fn domains first contract in the crowded environment of fibers within seconds into random coil conformations (molten globule states), before the force-bearing hydrogen bond networks that stabilize the domain's secondary structures are reestablished within minutes (double exponential). The exposure of cryptic binding sites on Fn type III modules increases steeply upon stretching. Thus fiber extension steadily up-regulates fiber rigidity and cryptic epitope exposure, both of which are known to differentially alter cell behavior. Finally, since stress-strain relationships cannot directly be measured in native extracellular matrix (ECM), the stress-strain curves were correlated with stretch-induced alterations of intramolecular fluorescence resonance energy transfer (FRET) obtained from trace amounts of Fn probes (mechanical strain sensors) that can be incorporated into native ECM. Physiological implications of the extraordinary extensibility of Fn fibers and contraction kinetics are discussed.fibrillogenesis ͉ matrix biology ͉ mechanotransduction ͉ multimodular proteins ͉ supramolecular assembly

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Retinal vein occlusion is an obstruction of blood flow due to clot formation in the retinal vasculature, and is among the most common causes of vision loss. Currently, the most promising therapy involves injection of t-PA directly into small and delicate retinal vessels. This procedure requires surgical skills at the limits of human performance. In this paper, targeted retinal drug delivery with wireless magnetic microrobots is proposed. We focus on four fundamental issues involved in the development of such a system: biocompatible coating of magnetic microrobots, diffusion-based drug delivery, characterization of forces needed to puncture retinal veins, and wireless magnetic force generation. We conclude that targeted drug delivery with magnetic microrobots is feasible from an engineering perspective, and the idea should now be explored for clinical efficacy.

The first three-axis micro-force sensor with adjustable force range from ±20 μN to ±200 μN and sub-micro-Newton measurement uncertainty is presented. The sensor design, the readout electronics, the sensor characterization and an uncertainty analysis for the force predictions are described. A novel microfabrication process based on a double silicon-on-insulator (SOI) substrate has been developed enabling a major reduction in the fabrication complexity of multi-axis sensors and actuators.