Nanomedicine, Volume I: Basic Capabilities

© 1999 Robert A. Freitas Jr. All Rights Reserved.

Robert A. Freitas Jr., Nanomedicine, Volume I: Basic Capabilities, Landes Bioscience, Georgetown, TX, 1999


 

5.3.6 Presentation Semaphores

It will often be necessary to modify nanorobot surface biochemical characteristics, as for example to present self-antigen to ensure biocompatibility (Sections 15.2.3.3-15.2.3.6), to present targeted non-self-antigens to facilitate cytocarriage (Section 9.4.7) or elimination from the body (Chapter 16), or to create a traveling solvation wave (e.g., hydrophilic, lipophilic) on the nanorobot exterior surface to facilitate cytopenetration (Section 9.4.5.3). At concentrations of 1-10 nanomolar, there are 104-105 MHC Class I plasma membrane molecules per typical tissue cell, or ~10 MHC proteins/micron2 at the cell surface (Section 8.5.2.1).*


* As few as 210-340 MHC Class II/peptide complexes per antigen-presenting cell (~0.1 molecules/micron2) are needed to stimulate T cell interleukin-2 production3456 and a minimum of ~0.2 molecules/micron2 of agonist MHC/peptide complex can trigger proliferation and immunological synapse formation,3453 although a threshold density of >~60 molecules/micron2 of accumulated MHC-peptide complexes are required for full T cell activation.3453


The MHC Class I molecule (Section 8.5.2.1) consists of a ~45,000 dalton glycosylated polypeptide chain crudely shaped like a "hand" which is noncovalently grasping a 12,000 dalton nonglycosylated peptide microglobulin (Fig. 8.33). Eliminating anchor and attachment components which do not participate in recognition leaves an active antigen "semaphore" component measuring roughly 3 nm x 6 nm x 8 nm that must protrude from the cell surface.

To present this semaphore to the external environment at a nanorobot surface, a device roughly analogous to the manipulator arm described in Section 9.3.1.4 may be used. The manipulator arm includes a 7-nm diameter internal tool transport channel which can allow presentation and exchange of MHC-like molecules mounted on diamondoid jigs to the ~700 nm2 device tip, where they may be locked into position for temporary display. Total presentation mechanism volume is ~105 nm3, plus ~200 nm3 per antigen stored on board. Staggered arrays of presentation ligands mounted on pistons can create nanorobot surfaces with controlled spatially structured chemical characteristics (Fig. 5.18).

An alternative method involves a two-roller mill-type device using a continuous conveyor belt 80 nm in length with 10 antigen-binding jigs mounted on the belt spaced ~5 nm apart. An opening at one end allows exposure of one antigen at a time to the external environment. Each of the 10 antigens, all of which may be different, are rotated into place as required, under computer control. As with the previous system, existing bound antigens may be exchanged internally using mill-like mechanisms. The core of the device measures 10 nm x 30 nm x 50 nm ~ 15,000 nm3, or ~50,000 nm3 including drive and control mechanisms and housing, with a ~300 nm2 presentation face. Assuming a ~105 watt/m3 power requirement (Section 6.5.6), power dissipation is ~10-17 watts per semaphore or ~0.03 pW/micron2.

Either semaphore device has an external presentation surface area <1000 nm2. Providing the requisite ~10 antigens/micron2 requires at most ~1% of nanorobot surface committed to semaphores, or ~0.1% of the volume of a 1 micron3 nanorobot for all semaphore devices, excluding antigen storage.

 


Last updated on 16 April 2004