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 Inmessaging from Cells

Nanodevices can receive the natural chemical messages transmitted from and between cells simply by eavesdropping on the natural molecular message traffic. (Of course, mechanical (e.g., cytoskeletal) and electrical (e.g., ionic) cellular emanations may also be detectable by nanodevices.)

For instance, consider a ~0.1 micromole puff of epinephrine (aka. adrenalin, C9H13NO3, MW = 183 daltons) released into the human bloodstream from cells in the adrenal medulla located above the kidneys. Epinephrine is an emergency hormone emitted in response to stressful conditions which acts to increase heart rate, decrease the blood flow to the gut, increase blood flow to skeletal muscles, increase circulation of oxygen and nutrients to other organs, and mobilize the production of metabolic fuels such as fatty acids and glucose (by causing liver and muscle cells to break down glycogen) -- establishing the primitive mammalian "fight or flight" response.

As bloodstream concentrations rise over 1-10 sec to a peak of cligand ~ 10-8 molecules/nm3 (Appendix B), then from Eqn. 4.3 a bloodborne nanorobot with a single epinephrine chemical sensor having just ~0.4 nm2 of active surface area can detect the peak concentration in tEQ ~ 0.3 sec. A patch of 260 such receptors measuring ~500 nm2 in total physical surface area can detect the peak concentration within ~1 millisec of its occurrence, or can detect 10% of peak concentration within 10 millisec from the start of the ramp-up. Epinephrine and most other signaling molecules cannot be directly measured by nanorobots stationed within the cytosol because the molecule is hydrophilic and cannot pass through the cellular membrane (unlike the steroids). For the most rapid possible response to changing hormone levels, chemosensor-equipped nanorobots should be positioned on or inside the cells and organs which produce specific signals of interest, with the results of positive detections of increased activity quickly passed along through the in vivo communications network (Section 7.3).

For the rarest cytokines or steroid hormones present at cligand ~ 10-12 molecules/nm3 in the bloodstream or cytosol (equivalent to ~8 molecules inside one (20 micron)3 tissue cell or ~1 molecule inside a single leukocyte), a ~5000 nm2 sensor patch containing ~100 individual receptors (each having ~6 nm2 of active area) can register a detection in ~10 sec for a single cytosol-based nanorobot. However, cellular signaling molecules are more commonly present in the cytosol at ~10-8 molecule/nm3 levels,531 enabling ~1 millisec detections using this sensor configuration. By comparison, the typical target tissue cell has ~10,000 steroid receptors (each binding one steroid molecule) floating in the cytosol.

Nanodevices may also eavesdrop on morphogenic signals. For example, simple changes in the extracellular protease/antiprotease concentration ratio (which causes endothelial cells to detach from their parent vessel and invade their underlying stroma during angiogenesis) are readily detected using chemical nanosensors. Continuous monitoring of the relevant natural cytokine traffic can help nanorobots maintain a complete picture of current cellular activities and states. Indeed, the principal design challenge is likely to be sensory traffic data management rather than sensor speed or specificity. Living cells are awash in a sea of messages from hormones, cytokines, growth factors, and a host of other message-carrying molecules, all of which must be transmitted through complex chemical networks of intermediates and multiple signal pathways into the cell's interior.


Last updated on 19 February 2003