Nanomedicine, Volume IIA: Biocompatibility

© 2003 Robert A. Freitas Jr. All Rights Reserved.

Robert A. Freitas Jr., Nanomedicine, Volume IIA: Biocompatibility, Landes Bioscience, Georgetown, TX, 2003 Mechanically-Induced Proteolysis, Apoptosis, or Prionosis

Might intracellular mechanical or electrical activities of medical nanorobots damage cytosolic proteins leading to locally accelerated proteolysis, or trigger other processes that might increase the protein turnover rate? One recent study [4414] found that bovine pericardium tissue subjected to dynamic stress (such as might be imposed by nanorobot activities) experienced accelerated local proteolysis as compared to the same tissue subjected to static mechanical loads of equal magnitude. For example, the intracellular level of alphaB-crystallin, a small heat shock protein produced by human trabecular network cells, temporarily declines by 90% one hour after the cells are subjected to a single 10% linear stretch, due to an increased degradation rate of the protein [4415]. Cyclic tension force also induces ECM degradation in cultured chondrocytes [4416].

On the other hand, the protein turnover rate of myosin heavy chains in cultured rat myocytes is unaffected by changes in the contractile activity of the cell [4417], and continuous electrical stimulation at 10 Hz does not alter the rabbit muscle protein turnover rate although static stretch significantly increases protein synthesis [4418]. Cells in rat hearts subjected to a doubling of aortic pressure experienced a decrease in protein degradation – mechanical stretch restrained proteolysis [4419] – but another study [4420] found that the net rate of proteolysis in isolated rat hearts is not effected by mechanical workload. More research is required to resolve these issues.

Nanorobot mechanical activities that might lead to unintentional apoptosis (Section must be avoided. For example, detachment of tissue cells from ECM contacts [3964], manipulation of cell shape [3965], high intensity (~540,000 W/m2 at 750 KHz) ultrasound irradiation of cells [4392], significant physical damage to DNA [4421], and other mechanical cellular trauma [4422] have been shown experimentally to induce apoptosis. One study [4423] found that mechanical trauma to rat motor neurons increased the production of ubiquitin, which targets many intracellular proteins for degradation, and decreased the production of hsp70, an inhibitor of apoptosis. Cell containerization might trigger apoptosis (Section, as might mitochondrial or nuclear rupture (Section or intracellular acoustic cavitation (Section Related alternative modes of programmed cell death such as autophagy [5483] must also be avoided.

If apoptosis is triggered, it may be rapidly aborted by in cyto nanorobots. Inhibitors of apoptosis (Section are well known [4424-4430] that jam the caspases and other molecules involved in the cascade, and the anti-apoptotic effects of certain fullerene-based (Section and dendrimeric [5186] pharmaceuticals has already been described. Similar substances could be released, as appropriate, by medical nanorobots. Surface presentation of specific peptides can also prevent apoptotic activity, as in NK cells (Section Alternatively, in cyto nanorobots could abort an unwanted incipient apoptotic cascade by using molecular sorting rotors (Section 3.4.2) to quickly extract from the cytosol key apoptotic regulatory, mediator, or trigger molecules (e.g., cytochrome c), analogous to previous discussions of complement (Section, inflammatory (Section 15.2.4), coagulation (Section 15.2.5), and pyrogenic (Section 15.2.7) factor depletion by medical nanorobots.

Finally, care must be taken that exterior nanorobot surfaces or mechanical operations do not inadvertently induce pathological protein folding conformations [5916], as in amyloidosis and prionosis [4431-4434]. It is not yet known whether this still-speculative process is a significant risk in nanorobotic medical missions.


Last updated on 30 April 2004