The more we learn about mastering nature, the more we seem to learn that nature is the ideal model. For instance, everything from the lustrous lining of an abalone shell to the delicate tracery of a nerve strand assembles itself from garden-variety raw materials, atom by atom and molecule by molecule. That fundamental biological ability is what nanotechnologists desperately wish to imitate and, being human, even wish to improve on as they labor to create medically useful structures at dimensions as tiny as a nanometer—about one fifty-thousandth the width of a human hair.
Many artificial nanostructures, such as carbon nanotubes (cylindrical siblings of the famous buckyball) or quantum dots, can already be built, but only in extreme environments characterized by hard vacuums, high-intensity radiation, or directed electron beams. Yet when natural systems form nanoscale structures, “they do not require huge chemical plants or inputs of energy,” says chemist Fiona Case of Case Scientific in Vermont. “Nature’s structures are formed at room temperature using the same amount of energy released from a slice of pizza.”
How do the basic components of living systems construct themselves in such stunning variety, yet with such unerring precision and with so little energy? Scientists are gradually beginning to discover—and exploit—the rules of autonomous self-organization. Many researchers believe that sort of kinder, gentler dynamic self-assembly will soon be widely available, as scientists learn to nanoengineer more chemicals that can combine only in certain specific orientations, like Lego blocks. Some of the most dramatic accomplishments to date employ self-assembling artificial materials to promote complex biological repair.
At Northwestern University, chemist Samuel Stupp and his research team have developed various types of amphiphile molecules (each end is chemically attracted to a different kind of material) that form self-assembling nanofibers, which in turn can prompt the regeneration of bone and brain cells. Last spring the team reported that their fibers induced the formation of new blood vessels in both cell cultures and living animals. The molecules start out suspended in liquid, but once they are placed in living tissue and touch a cell, they begin to arrange themselves into a fiber matrix that forms a gel. The gel can then be designed to bathe the site in healing proteins.
Another technique involves building nanoframeworks that cause components to arrange themselves in desired designs. Last summer scientists at Technion-Israel Institute of Technology, with their colleagues at MIT, announced that they had grown muscle tissue from scratch and then implanted it into a living mouse—where it worked just like the real thing. They first devised a nanoscale plastic scaffold and then seeded it with common muscle precursor cells called myoblasts, along with endothelial cells of the sort found on the inside of blood vessels. Guided by the scaffold pattern, the ensemble promptly organized itself into elongated muscle strands, complete with onboard arteries and veins.
“We are on the verge of a materials revolution,” chemical engineer Sharon Glotzer of the University of Michigan declared recently in Science, “in which entirely new classes of ‘supermolecules’ and particles will be designed and fabricated with desired features, including programmable instructions for assembly.”
While some scientists are gradually training artificial nanostuff to build living stuff, others are exploring the flip side of self-assembly: employing natural systems to guide the construction of artificial devices. Chad Mirkin, another chemist at Northwestern, is investigating new ways to harness the special rule-based properties of DNA to build nanostructures. DNA is made of four substances—the nucleotide bases adenine, guanine, thymine, and cytosine—that will combine only in specific configurations and sequences. Thanks to them, your cells consistently produce proteins to the exacting specifications that life requires. Mirkin’s group uses customized DNA strands as templates to steer compounds into forming themselves into the right patterns for use as electronic circuits or catalysts.
“Nature has been using DNA for billions of years to ensure that certain chemical sequences arrange themselves only in certain ways and not in others,” says Mirkin. “And nowadays it can be routinely synthesized.”
Indeed, as nanoscience progresses, and as researchers gradually learn to mimic—if not control—the elegant and efficient ways in which biological systems create order from disorder, the familiar distinction between “natural” and “artificial” will grow increasingly tenuous. And in some areas, like the medical repair of damaged tissues, it may soon cease to matter.
Chad Mirkin, director of the International Institute of Nanotechnology at Northwestern University, and his colleagues are changing the future of diagnostic medicine with two nanoscale technologies. The first, called bio-bar-code assays, relies on nanoparticles designed to attach themselves to specific disease-causing proteins; these will vastly improve a doctor’s ability to detect diseases like cancer and Alzheimer’s in their early stages and to identify pathogens like anthrax. The second technology, called dip-pen nanolithography, works like an array of minuscule fountain pens that lay down lines 15 nanometers wide of practically any soluble material on a surface. The idea is to lay down a tiny strip of genetic material on a chip, to which only specific pieces of DNA can bind, and then stick a sensor on each side of it. If the target germ is present, its DNA will adhere to the strand on the chip and change its chemical properties, thereby triggering a warning signal.
Gene chips are not news.
What’s special about these?
M: Dip-pen nanolithography will allow researchers to prepare the highest-density gene chips the world has ever seen. A Holy Grail in this area is to create one chip capable of detecting any DNA sequence. To do this, one needs a spot of DNA for every possible combination of a 17-base-long sequence [enough to identify key elements of a germ genome]. That’s 417, or nearly 20 billion spots. With current microscale technology, this chip would be the size of a tennis court or at the very best a large-car parking space—too big to ever be practical. But with the resolution afforded by dip-pen nanolithography, one can prepare that kind of sensor chip in an area about the size of a penny.
So with these technologies a physical might take no longer than a minute?
M: Bio-bar-code assays have been used to detect biological markers for HIV, Alzheimer’s disease, mad cow disease, prostate cancer, and ovarian cancer. They will have major applications in blood screening, bioterrorism defense, infectious-disease screening, and cancer research. Conventional technology does not have the sensitivity to identify such markers in the blood, let alone to quantify their amounts. Once it is completely developed, such sensor technology should make it possible for a doctor or other individual to screen a patient for many infectious and genetic diseases in the course of an ordinary office visit.