The Science of Microscopic Folding
The core principle behind creating microscopic folded structures is a technique known as DNA origami. This method uses the natural base-pairing properties of DNA to build precise two- and three-dimensional objects. The process begins with a long, single strand of DNA, often sourced from a virus, which acts as a scaffold. Scientists then design hundreds of shorter DNA strands, called “staple strands,” which are engineered to bind to specific parts of the long scaffold strand.
When mixed in a solution under controlled temperature changes, the short staple strands pull different parts of the long scaffold together. This process forces the scaffold to fold into a predetermined shape, which can range from simple geometric forms to complex designs like boxes or wireframe polyhedrons. The result is a stable, nanoscale object with every detail of its structure precisely programmed by the sequence of the staple strands.
Specialized computer software, such as caDNAno, assists in this design process by allowing researchers to map out the exact folding path and determine the sequences for each staple strand. While DNA is the most common material due to its predictable binding and biocompatibility, researchers also explore using other polymers to create similar self-folding nanoarchitectures.
Activating and Controlling Origami Cells
These self-assembled structures are not static objects; they are designed to be dynamic and responsive. Their ability to change shape or perform an action is governed by specific environmental triggers intentionally engineered into their design. This allows a folded structure to transition from a closed to an open state, enabling it to perform a function at a precise time and location.
One common activation method involves changes in pH, the measure of acidity in a solution. A structure can be designed with a molecular “latch” that is sensitive to pH. This latch might consist of DNA sequences that form a stable triplex structure in an acidic environment, locking the object into a closed shape. When the environment becomes less acidic, the triplex dissolves, the latch opens, and the structure unfolds or releases its contents.
Light is another trigger for controlling these nanostructures. In some systems, light is used to change the acidity of the surrounding solution on command. Shining a light of a specific frequency can make the solution more acidic to close a nano-hinge, and turning the light off reverses the effect. Temperature is also used to control shape changes, as the binding strength of DNA strands is temperature-dependent. By heating or cooling the environment, scientists can induce or reverse the folding of these devices.
Real-World Applications
One of the most researched applications for this technology is targeted drug delivery. An origami structure is constructed as a hollow container, such as a box or tube, that can be loaded with a therapeutic payload like chemotherapy drugs. This nanocarrier is designed to remain closed as it travels through the bloodstream, protecting healthy tissues from the drug.
The container is engineered to open and release its contents only when it encounters a specific molecular trigger, such as a protein found on the surface of a cancer cell. For example, a DNA nanorobot loaded with thrombin, a blood-clotting enzyme, can be designed to seek out tumor blood vessels. Upon binding to a target protein on these vessels, the nanorobot opens, releasing the thrombin to create a clot that cuts off the tumor’s blood supply.
Beyond drug delivery, these structures are being developed as biosensors. An origami device can be designed to change its shape or emit a fluorescent signal when it binds to a specific molecule, such as a virus or a biomarker for a disease. For example, a sensor could be built to detect a particular strand of RNA. When the target RNA binds to a probe on the origami structure, it causes a conformational change that can be observed with specialized microscopy.
Building Complex Structures
The principles of self-assembly extend beyond single units to the construction of larger, more complex systems. Individual folded units can be designed with complementary “sticky ends,” which are short, single-stranded DNA overhangs that allow them to connect in a predetermined pattern. This hierarchical assembly process is analogous to biological systems where cells combine to form tissues. Researchers can program these interactions to build large lattices or three-dimensional structures from basic origami building blocks.
This capability allows for the development of “smart materials” whose properties can be altered on demand. By incorporating dynamic elements into the individual units, a larger assembled structure could change its overall shape or stiffness in response to an external signal. For example, a lattice built from switchable origami units could be made to expand or contract, functioning as a type of molecular muscle.
The assembly of multiple, coordinated parts lays the groundwork for creating microscopic robots. Different origami components, each designed for a specific task like a motor, a cargo container, or a sensor, could be combined into a single, functional system. These nanorobots could be programmed to work together to perform complex tasks, such as repairing tissues at the cellular level or assembling other nanoscale structures.