ABSTRACT
Events following Denervation and Reinnervation ........................................ 371 15.3.1 Neuromuscular Transmission ........................................................... 372 15.3.2 Muscle Fiber End Plate ..................................................................... 373 15.3.3 Extracellular Matrix ......................................................................... 374 15.3.4 Denervation Changes in Muscle Fibers ............................................ 376 15.3.5 Peripheral Nerve Regeneration ......................................................... 377 15.3.6 Summary .......................................................................................... 379
15.4 Role of Molecular Motors and the Cytoskeleton during Growth of a Nerve Axon ............................................................................................ 379 15.4.1 Summary .......................................................................................... 382
15.5 Coordination of Cytoskeletal Changes and Molecular Motors by Cell Signaling .......................................................................................... 383
15.6 Molecular Motors in Nanobiotechnology ..................................................... 385 15.7 Conclusions ................................................................................................... 386 Acknowledgments .................................................................................................. 386 References .............................................................................................................. 387
The ability of autonomous damage recovery, characteristic of any self-healing material (Amendola and Meneghetti, 2009), is an inherent property of living organisms. Many aspects of this self-healing occur on the nanoscale and depend on the coordinated action of a range of cellular nanomachines powered by high-energy phosphate compounds such as adenosine triphosphate (ATP). A prerequisite for this capability of living organisms is the fact that they are kept in a state far from equilibrium by the continuous supply of high-energy phosphate compounds as a result of the metabolism of carbohydrates, lipids, and proteins. Since the self-healing processes in living systems have been ˜ne-tuned by evolution, they should provide many important insights of value for the design and production of arti˜cial nanoscale self-healing systems. As for many other aspects of life, self-healing occurs at different levels of organization, from the molecular level to the levels of tissues and body parts. Self-healing at the molecular level includes the continuously ongoing DNA repair (Lindahl, 1993; Sancar et al., 2004), protein refolding (Saibil and Ranson, 2002; Kinbara and Aida, 2005), and other types of repair or regeneration of protein function (Barber and Andersson, 1992; Rando, 2001). Another continuously ongoing repair process within living cells is the turnover of most proteins on a daily to monthly basis. This is made possible by the tagging of nonfunctional proteins for destruction (Hershko and Ciechanover, 1998) and the existence of a DNA template and protein synthesis machinery (ribosomes) for producing new protein components on demand. These processes may be strongly speeded up or modulated by damage to the cell. On a higher level, there is continuous turnover of entire cells and tissues (e.g., in the gastrointestinal tract, the blood, and the skin). This is enabled by the presence of certain stem cells that continuously divide, and whose daughter cells, differentiate and distribute in a manner carefully regulated by various extracellular cues. Upon acute damage, for example, a skin wound, several processes start to counteract deleterious effects (e.g., infection, ·uid and electrolyte imbalances), remove the damaged tissue, and ˜nally restore the tissue to its original form and function. The potency of this process is clearly demonstrated in lower vertebrates, for example, lizards that may lose entire body parts followed by ordered regeneration.
