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

Robert A. Freitas Jr., Nanomedicine, Volume IIA: Biocompatibility, Landes Bioscience, Georgetown, TX, 2003

15.5.7.5 Mechanical Disruption of Intracellular Microzones

Intracellular compartmentation of metabolites without enclosure by membranes (i.e., physiologically persistent, localized, and essential intracellular chemical gradients) of low molecular weight species such as O₂ [4405, 5935, 5936], sodium [5937, 5938], potassium [5937, 5938], calcium [5939], amino acids [5937, 5940], sugars [5937, 5940], carbohydrate metabolism [4405], ATP [4404, 4405, 5936, 5937], and pH [4405, 5941] have been measured inside living cells [4404, 4405, 5937], although there appears to be no gradient between bulk cytosolic and submembrane ATP in Xenopus oocytes [5942]. Even erythrocytes, known to be devoid of intracellular organelles, can sequester ATP [4406]. Intracellular biochemical gradients due to normal physiological processes and protein crowding effects also were discussed in Section 8.5.3.3.

Sequential enzyme interaction complexity gives rise to substrate or metabolite channeling [4407] and compartmentation of macromolecules within specific regions of the cytosol [4408, 4409] or in association with specific components of the cytoskeleton [4410]. Regulated intracellular circulation systems may exist with cytoplasmic streaming rates from 1-80 microns/sec [4411]. Even water may be sequestered in microzones [5937]. Observations of transient intracellular hydrodynamics in the microorganism Dictyostelium discoideum have revealed the presence of a microscopic region near the cytosolic side of the plasma membrane where the mobility of water molecules is severely restricted [4412]. “The creation of specialized microzones of metabolism in accordance with their association with cellular organelles or membranal structures may be integral to normal function and regulation of adult mammalian cells.”[4405] These stable microzones could be disrupted by the passage of intracellular motile nanorobots, possibly causing disorganization of local cell metabolism and temporarily disturbing normal cellular homeostasis. Cytosolic leakage following microinjection (a crude analog to nanorobotic cytopenetration; Section 9.4.5) has also been observed to give rise to artifactual intracellular diffusion gradients [4413].

Once we fully understand how cells create and maintain microzones or cellular microdomains, we will be able to design nanorobots that can avoid disruption of these natural mechanisms, or repair such disruptions after they have occurred.

Last updated on 30 April 2004