DNA Technologies

August 22, 2005
The versatile DNA molecule has proven to be a powerful technological building block. Researchers have developed ways of combining DNA molecules that allow them to carry out computations in test tubes and create two-dimensional patterns and three-dimensional structures at the nanoscale.

Base-ics

Biological DNA is made up of strings of four types of bases - adenine, cytosine, guanine and thymine - attached to a sugar-phosphate backbone. Adenine pairs up with thymine and cytosine with guanine when two single strands of DNA combine to form DNAís familiar double helix shape.

Biological DNA acts as a code for producing the proteins that carry out lifeís processes. In a cellís nucleus, a DNA double helix opens to expose sections of single strands. Ribonucleic acid (RNA) makes a mirror copy of an exposed DNA strand, and the sequenced RNA serves as a template for producing proteins elsewhere in the cell.

Researchers can make artificial DNA that contains specific sequences of bases. These strands can interact to compute, and can assemble into specific shapes for nanomachines and templates for assembling other substances into devices or materials.

Operations

The basic biochemical operations used to manipulate DNA are restriction, hybridization, ligation and amplification. These operations are carried out by various enzymes. Restriction is the process of cutting strands after specific sequences of bases. Hybridization is the joining of two complementary single strands to form a double strand. Ligation is the joining of two strands at their ends. Amplification is the process of duplicating a strand many times.

Sticky ends, branches and tiles

The artificial DNA used in DNA computing and nanotechnology has a fundamental characteristic: sticky ends. Sticky ends are short sections of single-stranded DNA that extend beyond an end of a double-stranded DNA molecule. Matching sticky ends serve to join two pieces of double-stranded DNA.

Artificial DNA is usually configured in one of two basic building blocks: DNA tiles and four-armed branches. DNA tiles are made from four or six strands of DNA that repeatedly cross over each other to make two or three intertwined double helices. DNA tiles can be joined to form sheets. Branched DNA molecules consist of four single strands configured in a cross shape so that each branch is a double strand. Joining multiple branched molecules forms a two-dimensional lattice.

Computing

There are several ways of using DNA molecules to represent information and several ways to use the molecules to carry out computations. DNA sequences can be used to represent paths in route-optimization problems; DNA sequences can be mapped to strings of binary numbers and software strands can be programmed to carry out calculations on input strands; and DNA tiles can be constructed into Boolean logic circuits.

Traveling salesman

The first DNA computing problem, solved in 1994, used DNA sequences to represent cities in the traveling salesman problem, which is the challenge of plotting the best route through a number of cities. The problem cannot be solved by a mathematical formula, meaning that all possible routes must be examined one by one.

At the same time, the number of routes grows exponentially with the number of cities. While there are only 4 times 3 times 2 times 1, or 24, possible routes through five cities, the number grows to 362,880 with 10 cities, and 87,178,291,200 with 20 cities.

The 1994 DNA demo showed that it is possible to use DNA to find all of the routes through a set of five cities beginning and ending with a specific pair of cities and visiting each city only once.

Each path between two cities was assigned a unique 20-base DNA strand, and many copies of these strands were mixed and allowed to combine end to end. This generated strands of various lengths representing random routes. The next step was to weed out all strands except those that began and ended with the segments representing the designated start and end points. Next, all strands except those of the minimum length, meaning one segment per city pair, were removed. The last step was removing all strands that contained repeated segments, leaving only the DNA combinations that represented routes from the origin to the destination that passed through every city only once.

Software

A system of programmable DNA maps DNA sequences to symbols like binary numbers, uses software strands to carry out calculations and uses input strands that represent possible answers to a problem. The software DNA strand is programmed to combine with certain input strands and to direct enzymes to cut the attached input strands. The system goes through a cycle of joins and cuts, and ends by joining an input strand to one of two marker strands that indicate whether the input is correct or not.

Logic circuits

An approach that more closely mimics digital computers uses DNA tiles to configure basic logic circuits whose inputs and outputs represent the 1s and 0s of binary computing. Tiles representing input and output are designed to combine so that the output tiles represent the appropriate output of a logic gate for the given input.

Readout

DNA readout is typically carried out by the process of gel electrophoresis, which is often used to analyze biological DNA. DNA molecules naturally carry an electric charge, and placing DNA in a gel with electrodes at either end causes the DNA to move from the negative side of the gel toward the positive side. The speed of the movement is determined by the length of the molecule; the shortest molecules travel the furthest.

In computations like the traveling salesman problem, the lengths of the molecules correspond directly to the answers. In binary DNA computing, marker molecules of different lengths differentiate the answers. Scientists can then use DNA sequencing techniques on copies of the molecules to determine their compositions and see the answers. In logic circuits, recorder strands are imprinted with the coding for ones and zeros and strung together. The gel electrophoresis results directly correspond to the 1s and 0s of the answer.

Mechanics

It is possible to make machines from DNA molecules because the molecules can be made to change shape reversibly. Researchers have made tweezers that open and close and have fashioned several forms of rotary motors.

These machines usually consist of a configuration of DNA molecules in a particular shape, such as an open pair of tweezers. A single strand of a particular sequence of DNA combines with sticky ends on the DNA machine, causing the machine to change shape. In the case of DNA tweezers, the shape change puts a hairpin bend in the middle of the DNA molecule to draw the two halves of the molecule - the tweezer arms - closed.

A second strand that combines more readily with the first strand than the machine does usurps the first strand, removing it from the machine and returning the machine to its original configuration to complete the mechanical cycle.

Assembly

Tapping DNAís self-assembly abilities to build structures and devices from materials like carbon nanotubes and metal nanoparticles requires a way to attach the materials to specific DNA sequences. A common approach is to coat the materials with a particular protein, typically an antibody, that readily binds with another protein that in turn connects to a specific DNA sequence. This way, when DNA molecules combine to form programmed patterns, they also arrange the nanotubes or nanoparticles.


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