Course outline 1 Introduction 2 Theoretical background Biochemistry/molecular biology 3 Theoretical background computer science 4 History of the field 5 Splicing systems 6 P systems 7 Hairpins 8 Detection techniques 9 Micro technology introduction 10 Microchips and fluidics 11 Self assembly 12 Regulatory networks 13 Molecular motors 14 DNA nanowires 15 Protein computers 16 DNA computing - summery 17 Presentation of essay and discussion Introduction Sizes Organ Tissue Cell Molecule Atoms A cell is molecules Proper an organization communication between of millions these of molecules is essential to the normal functioning of the cell Structure provides an molecules communicate understanding of how Nanotechnology The creation of functional materials, devices and systems through control of matter at the scale of 1 to 100 nm, and the exploitation of novel properties and phenomena at the same scale. Self-assembling highly functional molecular machines aimed at performing specific tasks. Often highly ordered repeated patterns of a single functional unit. 1 nm = 0.0000000001 m or 0.0000001 mm Molecular machines ribosomes make proteins in cells protein DNA mRNA Molecular machines protein motors move material in cells ATP synthase rotor size: 10nm Nature, 386, 299 (1997) Protein motors Bacterial chemotaxis Bacterial chemotaxis Bacteria move using flagellar motors Protein network directs movement based on external conditions and random motion: attractants/repellents Simulate chemotaxis network (7 proteins) Bacterial chemotaxis Bacteria move towards chemical attractants and away from repellents Process: attractants/repellents bind to chemorecptors chemoreceptors transmit information to a central processing system central processing integrates many inputs and sends a signal to control flagellar motors Interesting sensitivity [ Pfeffer ] feature: adaptation of Movement of flagellar rotation Bacteria swim by rotating flagella Motor located at junction flagellum and cell envelope of Motor can rotate counterclockwise or CW clockwise CCW CW Bacterial motor Bacterial motor and drive train. Above: Rotationally averaged reconstruction of electron micrographs of purified hook-basal bodies. The rings seen in the image and labeled in the schematic diagram (right) are the L ring, P ring, MS ring, and C ring. (Digital print courtesy of David DeRosier, Brandeis University.) Biased random walk Bacteria swim smoothly for 1sec (30 m) tumble, change direction by an average of 60 deg Tumbling frequency Movement with respect to attractants: increasing concentrations less tumbling decreasing concentrations more tumbling Temporal or spatial regulation? [Koshland/Macnab] mix a bacterial suspension without attractant with solution containing attractant tumbling suppressed within a second bacteria swam for long distances in a straight line solution has regulation! no spatial gradient temporal Specifically, compares past second versus previous three seconds Information flow in chemotaxis Structure of the chemoreceptors ligand binding domain Chemotaxis protein network The flagella The flagella Microtublar motors Microtubule motor proteins Two main families of microtubule motor proteins carry out ATP-dependent movement along microtubules: 1. Kinesin: Most members of the kinesin family of motor proteins walk along microtubules toward the plus end, away from the centrosome (MTOC). 2. Dynein: The dyneins walk along microtubules toward the minus end (toward the centrosome). In each case there is postulated to be a reaction cycle similar (but not identical) to that of myosin. The motor domain undergoes conformational changes as ATP is bound and hydrolyzed, and products are released. Kinesins Kinesins are a large family of proteins with diverse structures. Mammalian cells have at least 40 different kinesin genes. The best studied is referred to as conventional kinesin, kinesin I, or simply kinesin. Some are referred proteins (KRPs). Kinesin I has a structure analogous distinct from that of myosin. There are 2 copies each of a heavy chain and a light chain. to as kinesin-related to but Kinesin I C-terminal tail domains light chains stalk domain N-terminal heavy chain motor domains (heads) hinge Kinesin I Each heavy chain of kinesin I includes a globular ATP-binding motor domain at the N-terminus. Stalk domains of heavy chains interact in an a-helical coiled coil that extends from heavy chain neck to tail. The coiled coil is interrupted by a few hinge regions that give flexibility to the otherwise stiff stalk domain. Kinesin I C-terminal tail domains light chains stalk domain N-terminal heavy chain motor domains (heads) hinge Kinesin I N-termini of the 2 light chains associate with the 2 heavy chains near the tail. The diagram above is over simplified. Light chains at the N-terminus include a series of hydrophobic heptad repeats predicted to interact with similar repeats in the heavy chains near the tail region, in a 4-helix coiled coil. Kinesin I C-terminal tail domains stalk domain light chains N-terminal heavy chain motor domains (heads) hinge Kinesin I C-terminal tail domains of kinesin light chains include several "tetratrico peptide repeats" (TPRs). The 34 amino acid TPRs mediate protein-protein interactions. Kinesin light chain TPRs are involved in binding of kinesins to cargo. C terminal domains of heavy chains may also participate in binding some kinesins to cargo. Cargo proteins bound by kinesins are diverse. microtubule Cargo scaffolding protein cargo vesicle kinesin receptor Some organelle membranes contain transmembrane receptor proteins that bind kinesins. Kinectin is an ER membrane receptor for kinesin-I. Scaffolding proteins, first identified as being involved in assembling signal protein complexes, mediate binding of kinesin light chains to some cargo proteins or receptors. Some membrane-associated Rab GTPases, that provide specificity for vesicle transport & fusion, are known to bind particular kinesins. Cargo scaffolding protein In absence kinesin of cargo, the kinesin heavy folds at hinge regions, bringing heavy chain tail domains receptor microtubule chain stalk cargo vesicle inactive kinesin into contact with the motor domains. In this folded over state kinesin exhibits decreased ATPase activity and diminished binding to microtubules. This may prevent wasteful hydrolysis of ATP by kinesin when it is not transporting cargo. Cargo scaffolding protein kinesin receptor microtubule Unfolding cargo vesicle inactive kinesin of kinesin into its more extended active conformation is promoted by: phosphorylation of kinesin light chains, catalyzed by a specific kinase, or binding of cargo. Kinesin transport Kinesin transporting a vesicle along a microtubule (+) microtubule (-) Observations of conventional kinesin transporting elongated particles have demonstrated that cargo particles do not roll along the microtubule. Instead kinesin walks maintaining the orientation of a cargo particle. along, Kinesin transport Kinesin transporting a vesicle along a microtubule (+) microtubule (-) Movement of the 2-headed kinesin is processive, meaning that it takes many steps without dissociating from a microtubule. A hand over hand reaction cycle involving the 2 heads has been proposed. Myosin V, which transports vesicles along actin filaments, also exhibits processive movement. Kinesin transport View an animation emphasizing the cycle of ATP binding, hydrolysis & product dissociation during processive movement of kinesin along a microtubule. Flagella Cilium plasma membrane Cilia & flagella are bounded by the plasma membrane. A basal body, which is a single axoneme centriole cylinder, is at the base of each cilium or flagellum. Cilia & flagella have a core axoneme, a complex of microtubules and associated proteins. Some distinctions: Flagella rotary basal body (centriole) cytosol are usually 1 or 2 per cell. They tend to have a or sinusoidal movement. They may have additional structures outside the core axoneme Cilia are usually many per cell. They tend to have a whip-like movement. Flagella plasma membrane B AA B radial spoke An axoneme includes: Nine doublet nexin link microtubules around the periphery. The dynein arm A tubule of each doublet has attached dynein arms. Two singlet microtubules, by a sheath. central surrounded Cilium cross section central sheath Nexin links & radial spokes. These provide elastic connections between microtubule doublets and between the A tubule of each doublet and the central sheath. Flagella Few mammalian cell types have motile cilia or flagella, including some respiratory epithelial cells and sperm cells. Many mammalian cells have a single short non-motile primary cilium. The photoreceptor structure of each retinal rod & cone cell develops from a non-motile cilium. DNA machines DNA secondary structures Secondary structures are made of base pairs. They are energy. stable with respect to free Nearest neighbor model (Zimm et al., 1964). Summing up stacking energies of adjacent base pairs and mismatched pairs Folding problem (Zuker et al., 1981) DNA secondary structures Base sequence (linear structure) 5’ 3’ Secondary structure folding 5’ TTC…GCA inverse folding 3’ Thermo-dynamical model Inverse folding problem (Hofacker et al., 1994). Optimization with the fold function for evaluation Search for sub-optimal structures (Wuchty et al., 1999). Enumeration of (sub-optimal) structures whose energy is under mfe+d Computation of the partition function (McCaskill, 1990). Computation of the frequency of a structure Estimation of the energy barier between structures (Flamm et al., 2000). DNA nanomachines Various DNA nanomachine DNA motor by B-Z transiton (Seeman et al., 1999) molecular tweezers (Yurke et al., 2000) three-state machine (Simmel et al., 2002) PX-JX2 (Yan et al., 2002) Hybridization inhibition by bulge loop (Tuberfield et al., 2003) Designing DNA sequence with bistable structures (Flamm et al., 2001) B-Z DNA nano-mechanical device Seeman, 1999 Yurke’s DNA tweezers Yurke’s DNA tweezers Yurke’s DNA tweezers Yurke’s DNA tweezers Yurke’s DNA tweezers Yurke’s DNA tweezers http://news.bbc.co.uk/1/hi/sci/tech/873097.stm Yurke’s DNA tweezers Simmel’s 3-state machine Yurke’s DNA tweezers Because and the thermodynamic paths for opening closing the molecular tweezers are different it is a thermodynamic engine. It is a clocked molecular motor. Biological molecular motors are catalysts that convert fuel to waist product. Hence, DNA systems in which interactions are catalytically controlled are of interest in devising free running DNA motors. Bulge loops Hybridization inhibition by bulge loops (Tuberfield et al., 2003) PX-JX2 by Yan Self-guided self-assembly DNA template for molecular motors A DNA lattice More complex patterns of motors on lattices can allow for sophisticated molecular robotics tasks. DNA template for molecular motors Motor Ab DNA tile A bifunctional antibody (Ab) is shown bound to a DNA aptamer on a tile and to a motor protein, thus immobilizing the motor onto the tile. DNA nano-mechanical device Walking triangles By binding the short red strand (top figure) versus the long red strand (bottom figure) the orientation of and distance between the triangular tiles is altered. These changes are observable by AFM. Applications Programmable state control for nano-mechanical devices. Also as a visual output method. DNA nano-mechanical device 8 turns 180ْ ْ 10.5 turns DNA motor devices Designs for the first autonomous DNA nanomechanical devices that execute cycles of motion without external environmental changes. Rolling DNA device uses hybridization energy Walking DNA device uses ATP consumption These DNA devices translate across a circular strand of ssDNA and rotate simultaneously. Generate random bidirectional movements that acquire after n steps an expected translational deviation of O(n1/2). Reif, 2002 DNA motor devices Walking DNA device Rolling DNA device Rolling DNA Device Walking DNA Devi ce dsDNA Walk er dsDNA : walker ssDNA ssDNA road Road: ssDNA ssDNA ssDNA road dsDNA Roller:roller Road: Bidi rectionalTr ansl at ional Bidirectional translation and & Ro tati ona l Move me ntmovement rotation Bidirectional Random Translational& Rotational Movement Carbon nanotubes Molecular machines carbon nanotubes and buckyballs strong, light, flexible, electronic devices easy to make hard to arrange Carbon nanotubes Single sheet of graphite Strongest known fibers. 10-100 times more stronger than steel per unit weight Carbon nanotubes Can behave as a semiconductor or metal Nanomachines Nanomachines Molecular machines complex molecules for robot parts currently only theory hard to make hard to assemble potential: cheap, fast, strong parts example designs: E. Drexler, R. Merkle, A. Globus example medical applications: R. Freitas, Jr., Nanomedicine, 1999 Molecular mechanics Internuclear distance for bonds Angle (as in H2O) Torsion (rotation about a bond, C2H6 Inter-nuclear distance for van der Waals Spring constants for all of the above More terms used in many models Quite accurate in domain of parameterization Molecular mechanics Limitations Limited ability to deal with excited states Tunneling (actually a consequence of the pointmass assumption) Rapid nuclear movements reduce accuracy Large changes in electronic structure caused by small changes in nuclear position reduce accuracy Hydrocarbon bearing Hydrocarbon universal joint Rotary to linear NASA Ames Bucky gears NASA Ames Bearing Neon pump Applications Nanomedicine Disease and ill health are caused largely by damage at the molecular and cellular level Today’s surgical tools are huge and imprecise in comparison Nanomedicine In the future, we will have fleets of surgical tools that are molecular both in size and precision. We will also have computers much smaller than a single cell to guide those tools. Nanomedicine Size of a robotic arm ~100 nanometers 8-bit computer Mitochondrion ~1-2 by 0.1-0.5 microns Nanomedicine Mitochondrion Size of a robotic arm ~100 nanometers “Typical” cell: ~20 microns Typical cell Mitochondrion Molecular computer + peripherals Remove infections Clear obstructions Respirocytes http://www.foresight.org/Nanomedicine/Respirocytes.html Release and absorb ATP, other metabolites Na+, K+, Cl-, Ca++, other ions Neurotransmitters, hormones, signaling molecules Antibodies, immune system modulators Medications etc. Correcting DNA Nanomedicine Nanosensors, nanoscale scanning Power (fuel cells, other methods) Communication Navigation (location within the body) Manipulation and locomotion Computation http://www.foresight.org/Nanomedicine Nanomachines in biology Nanoscale machines already exist in biology,i.e. functional molecular components of cells. They exist in enormous variety and sophistication Biochemical motors Ribosomes make proteins in an assembly-line like (sequential) process Topoisomerase unwinds double-stranded DNA when it becomes too tightly bound Nanomachines in biology Self-replicating molecular nanomachines have already invaded just about every corner of the earth – they are called biological cells. They used atoms, molecules and energy forms to construct complex objects from the primeval soup Nanowires Introduction Molecular electronics www.scientificamerican.com Molecular electronics Biological Systems Molecular Electronics Devices Use molecular electronics to study biological systems. Molecular electronics Incentives Molecules are nano-scale Self assembly is achievable Very low-power operation Highly uniform devices Quantum Effect Devices Building quantum wells using molecules Electromechanical Devices Using mechanical switching of atoms or molecules Electrochemical Devices Chemical interactions to change shape or orientation Photoactive Devices Light frequency changes shape and orientation. Molecular electronics Definition is a field emerging around the premise that it is possible to build individual molecules that can perform functions identical to those of the key components of today’s microcircuits. Why molecular electronics? Chip-fabrication specialists will find it economically infeasible to continue scaling down microelectronics. stray signals on the chip the need to dissipate the heat from so many closely packed devices the difficulty of creating the devices in the first place Molecular electronics, any better? Modern technologies can only go so far. Solution (new development) DNA - It is promising to achieve super-high density memory and high sensitive detection technology. Cell Computing Silicon transistors at 120 nm in length will still be 60,000 times larger in area than molecular electronic devices. Recent research Recent studies have shown that individual molecules can conduct and switch electric current and store information. July of 1999 – HP and the University of California at Los Angeles build an electronic switch consisting of a layer of several million organic substance molecules of an called rotaxane. Linking a number of switches version of an AND gate is produced. a Recent research June 2002 - Fuji Xerox biotechnology made a prototype transistor of DNA from salmon sperm. Researchers successfully passed an electric current through the DNAtransistor. This demonstrates that behaves in a similar semiconductor. Super smaller chip in 10 years. the chain fashion to Recent research Atomic force microscope image of semi-conductive DNA compound http://www.fujixerox.co.jp/research/eng/category/inbt/m_electronics/index.html Self assembly Molecular self-assembly the autonomous organization of components into patterns or structures without human intervention (Whitesides 2002) Current Problem: Forming electrical interconnects between molecules Self assembly www.scientificamerican.com Molecular electronics Thiol Acetylene linkage Benzene ring Molecular electronics Mechanical synthesis Molecules aligned using a scanning tunneling microscope (STM) Fabrication done molecule by molecule using STM Chemical synthesis Molecules aligned in interactions Self assembly Parallel fabrication place by chemical an atomic relay A very short Electronics course Transistors A device composed of semiconductor material that amplifies a signal or opens or closes a circuit. Invented in 1947 at Bell Labs, transistors have become the key ingredient of all digital circuits, including computers. Today's microprocessors contains tens of millions of microscopic transistors. Transistors Transistors consist of three terminals; the source, the gate, and the drain. Transistors In the n-type transistor, both the source and the drain are negatively-charged and sit on a positively-charged well of psilicon. Transistors When positive voltage is applied to the gate, electrons in the p-silicon are attracted to the area under the gate forming an electron channel between the source and the drain. Transistors When positive voltage is applied to the drain, the electrons are pulled from the source to the drain. In this state the transistor is on. Transistors If the voltage at the gate is removed, electrons aren't attracted to the area between the source and drain. The pathway is broken and the transistor is turned off. DNA wires DNA Well known from biology Forms predictable structure Controllable self assembly through base pair sequences May be selectively processed using restriction enzymes http://www.chemicalgraphics.com/ DNA in microelectronics As the major component in a Single Electron Tunneling (SET) Transistor As tags to connect up nano-circuitry including wires and nanoparticles (taking advantage of DNA selectivity) As basis for computation) a Qubit (for quantum DNA SET transistor DNA Single electron transistor Main strand Gate strand Equivalent Electrical Circuit E. Ben-Jacob , Phys. Lett. A 263, 199 (1999). Main strand Assumptions Chemical bonds(in DNA) can act as tunnel junctions in the coulomb blockade regime, could emit electricity, given a proper coating. Has the ability to coat a DNA strand with metal in nanometer scale. Operation Schematic image with 2 grains in DNA connected by P-bond. Dark circle->carbon atoms, white circles>oxygen atoms. DNA pairs P-bond -> tunneling junction. H-bonds -> capacitor. The grain itself -> inductive properties. DNA pairs P bond: Has 2 bonds, 1 bond. The electron can be shared with 2 oxygen, resembles an electron in well, put it on the lowest level. When electron enters, it meet the barrier set by energy gap. But the gap is narrow and electron can walk trough. small so the DNA pairs H-bonds: Can be the capacitor. The proton in the h-bond can screen a net charge density on either side, by movement. Thus the net charge could be in the side of the h-bond. The grains: Can be the inductive properties. Due to the hopping of additional electrons. But can be ignored (L & Lo is small, consistent to the usual SET) DNA pairs Consist of 2 strands (1 main, 1 gate) Connect the end base of the gate strand with a complimentary strand. Both strands should be metal-coated, except (a) the grain in the main strand, which connect to the gate strand, the connective h-bond. 2 adjacent P-bonds, (b) Connect the main strand with voltage source (V) the DNA pairs The end of the gate strand with another voltage source (Vg) that acts as gate source. Functionalisation of nanoparticles DNA may be attached to surface area of nanoparticles to construct desired assemblies. May provide insight to possible solution to connecting transistors Functionalisation of nanoparticles Mirkin et al.: Nature, 1996, 382, 607 Functionalisation of nanoparticles Mirkin et al.: Nature, 1996, 382, 607 Functionalisation of nanoparticles 8 nm gold particles attached to a 31 nm gold particle with DNA http://www.chem.nwu.edu/~mkngrp/dnasubgr.html DNA conductance Double helix – a backbone and base pairs Building blocks A, T, C & G Example: 10 base pairs per turn, distance of 3.4 Angstroms between base pairs. Arbitrary sequences possible A challenge for nanotechnology is controlled / are the base pairs: reproducible growth. DNA is an example with some success. However, there are many copies in a solution! 2D and 3D structures with DNA base pairs as a building block have been demonstrated Lithography? Not yet. DNA base-pairs DNA conductance Conductivity in DNA has been controversial Electron transfer experiments (biochemistry) / possible link to cancer Transport experiments (physics) DNA conductance Metallic, No gap Current Current ~ 1nA ~ 10nA Semiconducting / Insulating Voltage (V) Porath et. al, Nature (2000) Voltage 20mV Fink et. al, Science (1999) Counter-ions Is conduction through the base pair or backbone? - Basepair When DNA is dried, where are the counter ions? Crystalline / non crystalline? Counter ions significantly modify the energy levels of the base pairs Counter-ion important Resistance species increases is also with length of the DNA (exponential within the of simple models) the sample context Counter-ions DNA-based metalised nanowires 10 nm wires: AuPd on DNA Needed Smaller wires and constructs Difficult to make conventional means Find if DNA is wires a good this scale substrate metalisation (and for which metals) Conducting and superconducting wires by for Which DNA? λ-DNA: double-stranded, 2 nm width, 16 micron length Poly-C, Poly-A, etc.: Single-stranded, all same base, 1 nm width Designed, complementary strands: Self assembly presents possibility for complex structures λ-DNA, uncoated: ~5 nm wires Metalised DNA 1) 2) Earlier construction of DNA-templated nanowires Braun Richter Nanotubes, other substrates 1: 100 nm thick wires, Ag on DNA 2: 50 nm thick wires, Pd on DNA E. Braun, Y.Eichen, U. Sivan, and G. Ben-Yoseph, Nature (London) 391, 775 (1998). J. Richter et al. Appl. Phys. Lett. 78, 536 (2001) Methods Suspend DNA across undercut 100 nm trench -or Suspend across cuts in thin (60 nm) membrane –variable width carved by focused ion beam Metalize by sputtering or evaporation Image with scanning electron microscope Make electrical measurements Methods Schematic of undercut trench Set-up Schematic of electrode overlaying wire Methods Hitachi 4700 Scanning Electron Microscope More metalised DNA-wires AuPd sputtered on λ DNA Osmium plasma coated on λ DNA Wires made repeatedly, variety of coatings (or none) Width range from <5 nm bare DNA wires to >30 nm heavily coated in AuPd. The thinnest contiguous wires are ~10 nm thick Metalised DNA-wires Variable width cuts in membrane, made by focused ion beam. DNA bridges the cuts. Longest wire to date: 960 nm (~30 nm thick) Appearance of multi-strand “Ropes” Metalised DNA-wires Multi-strand “rope,” 3 nm AuPd coating, total thickness: 3040 nm Length: 960 nm Two wires connected by “rope” visible on surface of membrane, length: 550 nm on right, 670 nm on left Is it functional? Measurement contacts produced photolithography techniques by Potentially superconducting or 3He system First Mo0.79Ge0.21 coated samples: superconductivity standard samples in 4He test for Not yet .... First MoGe sample weakly conductive, superconductivity- too thin! Room temperature: 2.3 MΩ, Lowest point: 750 kΩ, sharp upturn near usual critical temperature (near 4 K) Possible film Next samples: Si coat discontinuities or oxidation no of 7 nm MoGe with protective Variations More conductivity measurements Different DNA structures Normal and Device possibilities? As thin as possible (preferably functional) superconducting wires Variations Poly-C wire with 2 nm AuPd, total width: 5 nm. DNA template DNA templated electronics The DNA acts as a scaffold for positioning a single-walled carbon nanotube at the heart of a field-effect transistor, as well as a template for the metallic wires connecting the device. K Keren et al. 2003 Science 302 1380 DNA templated electronics DNA templated electronics What do we need to realise this assemble a DNA network localise moleculra scale electronic components transform DNA into conducting wires DNA templated wires silver wires formed on aldehyde derivitesed DNA continuous gold wires DNA templated gold wires wire width ~50nm DNA width ~2nm R~26 Ω Sequence specific molecular lithography Sequence specific molecular lithography RecA polymerised on DNA (cryo-TEM) 3-armed junction formation building blocks synapsis final product branch migration AFM image of 3-armed junction Sequence specific molecular lithography patterning of DNA metallization Sequence specific molecular lithography Sequence specific molecular lithography RecA nuleoprotein filament localised on aldehydederivatized DNA sample after silver deposition AFM sample after gold deposition SEM Sequence specific molecular lithography optical lithography molecular lithography Others Carbon nanotubes Carbon nanotubes The device - which consists of a single-walled carbon nanotube sandwiched between two gold electrodes operates at extremely fast microwave frequencies. The result is an important step in the effort to develop nanoelectronic components that could be used to replace silicon in a range of electronic applications (S Li et al. 2004 Nano Lett. 4 753). http://physicsweb.org/article/news/8/4/15 Superconductivity in nanotubes Left red data show insulating like behavior with resistance upturns at the lowest temperatures, blue data show superconducting behavior Right V-I data for a strongly superconducting sample at various temperatures. Courtesy, A. Bollinger Buckyball www.osti.gov/accomplishments/ smalley.html Cellular computing Cellular computing Goals To use a cell as the smallest DNA-based molecular computer More specifically, to mimic some or all of a cells mechanisms in order to produce a quasi molecular computer (QMC), or a true molecular computer (TMC) Quasi cellular computing Most of the input and output operations are driven by an external force Input and programming provided, QMC provides output All molecular computers are of this type, with the exception of the cell Goal for QMC’s: to develop QMC’s that are more efficient, and less dependent on outside interaction True cellular computing “All computational operations (input, output, state transitions) are driven by self organizing chemical reactions” (Ji 1999) All processes are internally driven, no outside help is needed Only known example is a cell Goal for TMC’s: to fabricate an artificial TMC with the properties of a living cell Cells versus computers Qualities of cells that are similar to those in computers Have inputs, state transitions, and outputs as indicated by their programming Have a language to communicate between cells Have information and energy storage mechanisms: IDS’s http://www.rkm.com.au/CELL/ Cells versus computers Cells Computers Current carried by: Chemicals Wires Reactions or Enzymes processes turned on or off by: Transistors Information stored in: Capacitors Biopolymers, IDS’s Computational DNA programs stored in: Software Cells versus computers Cells Computers Programmability No- not yet Yes SelfYes Reproducibility No- not yet Ji, Sungchul. The Cell as the Smallest DNA Based Molecular Computer. BioSystems (1999):52 123-133.