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

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

7.4.5.3 Outmessaging to Cells

Individual micron-scale nanorobots have insufficient chemical release volume or manufacturing capacity to transmit endocrine-like chemical signals throughout the entire bloodstream (Section 7.2.1.8), although simultaneous coordinated chemical releases may be made from large numbers of in vivo nanomachines for special purposes. Nanodevice outmessaging to cells thus will normally be limited to localized paracrine-like, neurotransmitter, or intracellular messaging, and of course nucleic molecules which may have a direct control function. Indeed, the most efficient outmessaging to cells may involve the assembly of customized RNA molecules or their antisense variants (using locally available raw materials such as RNA bases and amino acids) to up or downregulate specific gene activities (Chapter 12) thus taking advantage of the cell's inherent amplification by the ribosomes.

As a simple example, Ca⁺⁺ serves as an intracellular mediator in a wide variety of cell responses including secretion, cell proliferation, neurotransmission, cellular metabolism (when complexed to calmodulin), and signal cascade events that are regulated by calcium-calmodulin-dependent protein kinases and adenylate cyclases. The concentration of free Ca⁺⁺ in the extracellular fluid or in the cell's internal calcium sequestering compartment (which is loaded with a binding protein called calsequestrin) is ~10^-3 ions/nm.³ However, in the cytosol, free Ca⁺⁺ concentration varies from 6 x 10^-8 ions/nm³ for a resting cell up to 3 x 10^-6 ions/nm³ when the cell is activated by an extracellular signal; cytosolic levels > 10^-5 ions/nm³ may be toxic,⁵³¹ e.g., via apoptosis (Sections 10.4.1.1 and 10.4.2.1).

To transmit an artificial Ca⁺⁺ activation signal to a typical tissue cell in ~1 millisec, a single nanorobot stationed in the cytoplasm must promptly raise the cytosolic ion count from 480,000 Ca⁺⁺ ions to 24 million Ca⁺⁺ ions, a transfer rate of ~2.4 x 10¹⁰ ions/sec which may be accomplished using ~24,000 molecular sorting rotors (Section 3.4.2) operated in reverse, requiring a total nanorobot emission surface area of ~2.4 micron². Or, more compactly, pressurized venting or an ion nozzle may be employed (Section 9.2.7). Onboard storage volume of ~0.1 micron³ can hold ~2 billion calcium atoms, enough to transmit ~100 artificial Ca⁺⁺ signals into the cell after ionization (2877 zJ/ion double-ionization energy)⁷⁶³ even assuming no recycling.

In addition to the amplitude modulation (AM) of Ca⁺⁺ signals noted above, De Koninck and Schulman¹¹²¹ have discovered a mechanism (CaM kinase II) that transduces frequency-modulated (FM) Ca⁺⁺ intracellular signals in the range of 0.1-10 Hz. Fine tuning of the kinase's activity by both AM and FM signals (either of which is readily detected or generated by in cyto nanorobots) may occur as the molecule participates in the control of diverse cellular activities.

Nanorobots may also mechanically outmessage to cells. The cytoskeleton of living cells and nuclei are hardwired such that a mechanical tug on cell surface receptors can immediately change the organization of molecular structures inside the nucleus and the cytoplasm⁹⁴² and can dramatically alter cellular electrical conductivity.¹¹⁰⁰ The intermediate fiber network (Section 8.5.3.11) alone is sufficient to transmit mechanical stress to the nucleus.⁹⁴² The minimum force required to initiate signal transduction may be as low as ~10 pN (Section 9.4.3.2.1), well within the ~100 nanonewton capacity of the nanomanipulator arm described in Section 9.3.1.4.

Last updated on 19 February 2003