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 Biomechanical Computers

Components of mechanical computers could be constructed entirely of biologically-derived materials which in theory might be fabricated using synthesis pathways accessible to engineered microbiota. For example, Drexler's mechanical nanocomputer10 assumes diamondoid logic rods with a Young's modulus of E = 5 x 1011 N/m2, but the Young's modulus for human bone hydroxyapatite and fluoroapatite crystals is almost as high, with E ~ 1-2 x 1011 N/m2 (Table 9.3). Ignoring the significant problems inherent in noneutactic rod logic systems, apatite-based mechanical computer structures might be laid down using engineered osteocytes, perhaps assisted by chemotactic or contact guidance techniques. Failure strength of apatites is ~100 times poorer than for diamond, so apatite logic rod force and acceleration should be reduced by ~100 and rod vibrational energy by ~104, increasing minimum switching time by a factor of ~10 (to ~1 nanosec) and decreasing maximum rod speed to ~1 m/sec.

N. Seeman has constructed molecular building blocks from unusual DNA motifs (Section 2.3.1), using stable-branched DNA molecules with the connectivity of a cube1914 or a truncated octahedron.1915 E. Winfree1919 has proposed using arrays of DNA crossover molecules1920 in DNA-based computing, requiring the ability to build periodic backbones with bases differing from one unit cell to another. In addition to branching topology, DNA also allows control of linking topology. DNA-based topological control has led to the construction of Borromean rings which could be used in DNA-based computing applications.1916-1918 In Borromean rings, the linkage between any pair of rings disappears in the absence of the third. Rings can be designed with an arbitrary number of circles; the integrity of a link could represent the truth of each of a group of logical statements.1916

DNA structural transitions could be used to drive nanomechanical devices via branch migration.1916 Application of torque to a cruciform leads to the extrusion or intrusion of a cruciform.1921 A synthetic branched junction with two opposite arms linked can relocate its branch point in response to positive ethidium-induced supercoiling, representing the first experimental step in developing DNA structural transitions that can achieve a nanomechanical result.1922 The possible use of the B-Z transition (e.g., from right-handed B-DNA to left-handed Z-DNA) in nanomechanical devices is being explored.2409

In 1998, Winfree and colleagues in Seeman's laboratory1970 described a simple, predictable, highly precise technique for arranging DNA molecules into two-dimensional crystals. At the same time, a paper by Heath and others1980 described a defect-tolerant computer architecture called the Teramac, a massively parallel experimental computer which apparently could operate normally with at least half of its most critical components failed. The authors claimed this architecture showed it would be "feasible to chemically synthesize individual [molecular] electronic components with less than a 100% yield, assemble them into systems with appreciable uncertainty in their connectivity, and still create a powerful and reliable data communications network."

One can also imagine a network of interlocking enzyme-like conformational switches, possibly embedded in a sem-irigid two- or three-dimensional scaffolding of DNA1904,1913-1916 or protein1905,1913 molecules. Enzymes may display multivalent feedback inhibition (making a NAND gate; Section or may have multiple metal-ion binding sites influencing enzymatic action;1928 an enzyme requiring two conformational changes to inhibit its action could serve as a biomechanical NAND gate if tethered to other similar enzymes in an appropriately structured protein array.1905 Single-device error rates will be high but might be reduced to acceptable levels by employing short multiply-redundant pathways for each digital computational operation, or a sufficiently parallel architecture.1980 Site-directed mutagenesis optimization of antibodies has shown that natural proteins can be made significantly stiffer and more stable by the mutation of just a few amino acids. Systems of reciprocating actomyosin molecular motors (e.g., as found in muscle fibers; Section might serve as interdigitating components of a push-pull mechanical logic architecture resembling rod logic or a three-dimensional loom. In early 1999, Viola Vogel (University of Washington Center for Nanotechnology) and colleagues discovered, via computer simulation, a tension-activated fully-reversible biomechanical switch comprised of a single strand of fibronectin protein -- like untying a shoelace, a slight mechanical tug unravels a folded segment, switching off the protein's biochemical activity.3249

Mechanical coupling of intracellular Ca++ ion release channels allows coordinated voltage gating across the surface membrane of the sarcoplasmic reticulum inside muscle cells.1964 R. Bradbury [personal communication, 1999] suggests that site-directed mutagenesis could produce a family of proteins that could be activated by the release of various mono- (e.g., K+), di- (e.g., Ca++), and tri-valent (e.g., Al+++) ions. This would allow multivalued logic (e.g., K = 1, Ca = 2, Al = 4), or increased parallelism or bandwidth (e.g., Ca = !(K & K), Al = !(Ca & Ca), etc.); once a protein exists that can be activated by a single ion, then varying its architecture to allow substitution of an ion of different size or charge is a relatively straightforward engineering exercise. A biomechanical Turing machine design has also been reported by Shapiro.3247


Last updated on 24 February 2003