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 Intracellular Cavitation, Shock Waves, Decompression Nucleation, and Ballooning

Acoustic pistons operated in cyto for nanorobotic power transmission (Section 6.4.1) or communication (Section 7.2.2), or rapidly moving mechanical elements enabling intracellular manipulation (Section 9.3.1) or locomotion (Section 9.4.6), could induce transient cavitation inside the cell. Cavitation bubbles may produce temperature increases of ~1000 oC and pressure spikes of ~1000 atm localized in regions of a few microns in radius, and should be avoided during normal operations because they may elicit cellular apoptosis [4392]. Normal or transient cavitation requires ~105 W/m2 (~5.4 atm or ~550 nN/micron2) at 30 KHz or ~106 W/m2 (~17 atm or ~1700 nN/micron2) at 1 MHz in order to form in water [4393]. Intensities less than ~104 W/m2 will not produce transient cavitation in any tissue [4394].

Intracellular damage may also be caused by acoustic shock waves that could be generated by nanorobots or nanoaggregates. Individual cell components have different measured sensitivities to the energy density of applied acoustic pulses. For example, observable defects are produced in lipid membranes at acoustic energy densities as low as 120 J/m2; in vimentin (an intermediate filament cytoskeleton attachment protein) at 210 J/m2; in mitochondria at 330 J/m2; and in nuclear membranes at 500 J/m2. A loss of cells growing on a microcarrier was also observed after applying 200 pulses at 210 J/m2 per pulse [4395]. In another experiment [4396], pressure waves lasting 0.5-1.5 msec up to 250 KHz impacting on dorsal root ganglion nerve cells of rats showed negative changes in neurite microtubules within minutes. After 6 hours there was swelling of nerve cell cytoplasm and organelles, and some neurofilament tangles were observed. Even loud noise can produce transitory mechanically induced microlesions in the cell membranes of several types of nonauditory cells, a mild membrane wounding from which the cells can survive and functionally recover [4397].

Can rapid cell decompression cause internal bubbles? Sudden decompressions from up to 200 atm produce no intracellular bubble formation, in the absence of intracellular particles, in red blood cells, microbial cells, or pure water [4398, 4399]. Decompression bubbles form in cells of the ciliate Tetrahymena pyriformis that have ingested graphite particles from aqueous suspensions when tested with 10-50 atm nitrogen supersaturations, though it is possible to alter the surface of intracellular graphite particles to avoid intracellular gas bubble formation during decompressions from external pressures as high as 25 atm [4400]. Gas tensions of a few atm can cause profuse bubble nucleation if the most effective nucleation particles are used. But ingested effective-bubble-promoter particles lose their ability to induce bubble formation in cells, up to >~175 atm, when added to suspensions of ciliate microbes (and ingested by the microbes). Though we must be cautious extrapolating to human cells, if this result is not merely a property of the cellular interior (e.g., cytoskeletal structure) then it might imply that intracellular bubble formation during decompression is rare because particle surfaces are somehow chemically modified during the ingestion process, by the microbial cell [4399]. If nanorobot surfaces are designed to resist this sort of chemical modification, then the risk of bubble formation in these circumstances rises. When operating in pressurized living cells, nanorobot structure and function should be designed to minimize bubble nucleation during subsequent cellular decompression.

To what degree may an in cyto gas bubble or nanorobotic balloon expand before the cell bursts or is severely damaged? Experimental data are available for just a few unrelated cases. Skalak [4401] found that a red blood cell placed in hypotonic solution swells from its normal biconcave discoid shape into a sphere, reaching its osmotic bursting pressure at ~3.1 x 106 N/m2 (~31 atm). Internally-formed bubbles rupture Tetrahymena cells at 25-50 atm [4400], and mechanical cell homogenizers burst cell membranes by compressing cells to ~1500 atm, then passing them through a rapid decompression nozzle [4402]. A force of 20-220 mN (14-130 atm) was required to burst 0.7- to 7-micron dry microcapsules pressed between two flat surfaces [4403]. A similar experiment performed on relatively fragile wet hybridoma cells produced bursting at only 0.06 atm for 10-micron cells [4129].


Last updated on 30 April 2004