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IMM Report Number 29: Nanomedicine Volumetric Cellular Intrusiveness of Medical Nanorobots
In conjunction with Foresight Update 47
January, 2002
By Robert A. Freitas Jr.
Research Scientist, Zyvex Corp.

The fact that lipofuscin is an indigestible lipid peroxidation product that cannot be excreted, but whose presence is usually not injurious to the cell, argues strongly that cells can tolerate major volumetric replacements of protoplasm with artificial foreign bodies, such as medical nanorobots, while continuing to function normally.



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A useful and simple experiment that could be done today would be to microinject various cell types with progressively larger loads of chemically inert diamond microparticles, noting the effect (if any) on cell motility, behavior, and metabolic function.



Medical nanorobots on cytotherapeutic missions will often need to enter the living cell to perform repairs. Such missions may require the participation of many cooperating nanorobots, or perhaps just a few but relatively large nanorobots, per cell. And so the question logically arises: How many nanorobots can safely be crammed into a single living cell? There are at least two issues here. First, how much new foreign material can be added to a cell? Second, how much of a cell's existing volume can be replaced with foreign material with no change in total cell volume? Since we can't yet do direct experiments with medical nanorobots and living cells, no precise answer is possible. But we can estimate the maximum volume of foreign material that the intracellular compartment might safely accommodate by examining analogous instances of cellular intrusion.

We can start by considering cell membrane elasticity. How much can the cellular membrane stretch before it breaks? The introduction of foreign material into a cell may cause intracellular volume to expand. Assuming a spherical cell shape, the change in cell volume Δ Vcell from the original cell volume Vcell is related to the change in plasma membrane area Δ Acell of an unstretched membrane of area Acell by the relations Δ Vcell /Vcell ~ ((1 + Δ Acell/Acell)3/2 - 1) and Δ Acell/Acell = Tmemb / Kmemb, where Tmemb is the isotropic tension due to membrane expansion and the area compressibility modulus Kmemb = 0.378 N/m for erythrocyte plasma membrane at 310 K and Kmemb = 0.636 N/m for leukocyte plasma membrane ([1], Section 9.4.3.2.1). Taking a conservative lysis limit of Tmemb ~ 4 x 10-3 N/m for erythrocytes, then Δ Vcell /Vcell ~ 1.6% for red cells and ~0.9% for white cells. That's not much stretch.

However, erythrocytes are not spheres but biconcave disks with a mean volume of 94 micron in isotonic solution (300 mosmol). Red cells absorb water in hypotonic solution, becoming spherical at 131 mosmol with a volume of 164 micron, demonstrating a capacity for volumetric expansion of 74% without losing membrane integrity. Other cells may permit even more expansion. For example, taking Tmemb = 1.7 N/m and Kmemb = 1.3 N/m for TB/C3 hybridoma cells and Tmemb = 1.8 N/m and Kmemb = 1.2 N/m for NS1 myeloma cells [2], then Δ Vcell /Vcell ~ 250% for hybridomas and ~300% for myelomas. These estimates are crude at best because the lipid population of the plasma membrane is constantly changing and may enlarge or contract over time.
(More: Institute for Molecular Manufacturing News Source)
2002 © Robert A. Freitas Jr.

Regarding cell elasticity, an oversight seems to be that the cells needing repair would likely be -- ill. This being the case, elasticity might be variable, dependant not only upon the level of illness, but upon the fundamentals of the cell’s DNA structure -- as well as host habitat/environment, dietary and physical exertion habits, and the overall health of the individual. These criteria would likely expand/compress the limits of cellular endurance on the micrometer scale, but I’m sure further experimentation will bring these facts to light.

In order to touch more bases, perhaps the research dept should incorporate some sci-fi thinkers -- people who think more on the ‘what-if” side of the box than the ‘here it is’ side -- into their network. Other than that, the thought process displayed is coming along pretty well.

Dan