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

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

9.4.7.5 Navigation and Sensing

The nanorobotic pilot can directly access the high-resolution extracellular acoustic navigational grid (if such has been installed in the patient; Section 8.3.3) to establish absolute position and orientation of the cytovehicle within the human body, or may employ alternative positional or functional navigational cues as may be provided by the attending physician (Chapter 8). Chemosensory data (including tissue- and cell-recognition events) reaching the exterior surface of the piloted cell trigger natural internal biochemical cascades which are readily monitored and interpreted by in cyto nanorobots. Extracellular and ECM-related mechanosensory data and plasma membrane stretch sensor data produce similar recognizable internal biochemical and cytomechanical effects.

Eavesdropping on natural chemotactic signals is particularly effective. For instance, after leaving the blood vessels, neutrophils recognize biochemicals produced by bacteria and migrate toward a rising concentration. Laboratory demonstrations of neutrophil chemotaxis often use a concentration gradient of fMLP (n-formyl methionine-leucine-phenylalanine), a peptide chain produced by some bacteria, at ~0.1 nanomole/cm³.¹⁵⁵⁴ Chemotaxis also occurs among human T-lymphocytes in the presence of a 0.01-1 picomole/cm³ gradient of Met-enkephalin or b-endorphin.¹⁵¹² Chemotactic cytokines for leukocytes, macrophages, and fibroblasts -- many of which are tissue-specific (and thus additionally serve as an aid to navigation) or condition-specific (e.g., inflammation) -- are well-studied.^{767,1516,1565-1570}

Similarly, E. coli has chemosensory receptors (three different transmembrane methyl-accepting chemotaxis proteins or MCPs⁵³¹ located mostly in clusters at one pole of the cell.¹⁵⁴⁴ At least two cytoplasmic signaling proteins, CheA and CheW, are known to interact with chemosensors in vitro.^1544,1545 Various intracellular mediator protein molecules convey chemoreceptor signals by diffusion (across one cell length in ~200 millisec)¹⁵⁴⁶ to the flagellar motors, which drive the bacterium forward in 20-40 micron/sec bursts.⁴³⁷ MCPs respond to attractants and repellants in the extracellular environment. All these signals can be detected in cyto by an eavesdropping "piggybacking" nanorobotic pilot equipped with appropriate (membrane-penetrating) cytoplasmic chemosensors.

The nanorobotic pilot may also deploy loosely-tethered nanosensor remotes and insert them into the cytovehicle's plasma membrane, during or after cytopenetration. These nanosensors may employ simple mechanical plasma membrane locking (Section 9.4.5.2) or a stationary solvation wave pattern (Section 9.4.5.3) to straddle the plasma membrane, mimicking natural transmembrane integral proteins (Fig. 8.37), or could anchor one end of their transmembrane structure to the underlying cellular cortex. Such sensors could gather whatever extracellular thermal, mechanical, acoustic, chemical, or electromagnetic data might be required by the pilot for proper navigation and steering. The nanosensors are retrieved when the nanorobotic pilot exits the cytovehicle at the destination.

When macrophages and other leukocytic cells become infected, they express B7 (a co-stimulator molecule) on their plasma membrane surface which can be recognized by a T-cell CD28 receptor protein, triggering an immunologic response in the presence of surface-displayed antigen.¹⁵⁵⁶ Nanorobotic pilots should inspect the cell surface of all prospective cytovehicles for B7 and similar pathogenic flags prior to cytopenetration, so as not to unintentionally choose an infected cell for cytocarriage which could then spread the infection or become subject to immunosystem attack. If the cell subsequently becomes infected and begins expressing B7 or other warning substances during the journey, the nanorobotic pilot should abort the mission and steer the cytovehicle to a nearby disposal site, or implement immediate cytotherapeutic measures. Failing this, the pilot should abandon the vehicle at once.

Last updated on 22 February 2003