From molecular to macroscopic via the rational design of a self-assembled 3D DNA crystal

Abstract

Creating a macroscopic object, such as a crystal, with the microscopic molecular structure desired is a challenge. One promising approach is the use of macromolecules with robust three-dimensional motifs and sticky ends so that, by attaching to one another, they can form a periodic arrangement that can be investigated by crystallographic techniques. Zheng et al. use DNA for this purpose, arranged in a structural motif called a tensegrity triangle, and can grow crystals of the order of 200 micrometres in size, in which the positions of the atoms can be determined with a precision of 4 Å. The highly specific interaction between complementary DNA strands makes it possible to realize the desired and designed structure for the unit cell of the crystal. The latter also exhibits periodic holes, which could potentially be used to host biomolecules in a three-dimensional periodic arrangement, making it possible to determine their structure even if they do not crystallize on their own. Although we live in a macroscopic three-dimensional (3D) world, our best description of the structure of matter is at the atomic and molecular scale. Reconciling these two scales with atomic precision requires high spatial control of the 3D structure of matter, with the simplest practical route to achieving this being to form a crystalline arrangement by self-assembly. Here, the crystal structure of a designed, self-assembled 3D crystal based on the DNA tensegrity triangle is reported. We live in a macroscopic three-dimensional (3D) world, but our best description of the structure of matter is at the atomic and molecular scale. Understanding the relationship between the two scales requires a bridge from the molecular world to the macroscopic world. Connecting these two domains with atomic precision is a central goal of the natural sciences, but it requires high spatial control of the 3D structure of matter1. The simplest practical route to producing precisely designed 3D macroscopic objects is to form a crystalline arrangement by self-assembly, because such a periodic array has only conceptually simple requirements: a motif that has a robust 3D structure, dominant affinity interactions between parts of the motif when it self-associates, and predictable structures for these affinity interactions. Fulfilling these three criteria to produce a 3D periodic system is not easy, but should readily be achieved with well-structured branched DNA motifs tailed by sticky ends2. Complementary sticky ends associate with each other preferentially and assume the well-known B-DNA structure when they do so3; the helically repeating nature of DNA facilitates the construction of a periodic array. It is essential that the directions of propagation associated with the sticky ends do not share the same plane, but extend to form a 3D arrangement of matter. Here we report the crystal structure at 4 Å resolution of a designed, self-assembled, 3D crystal based on the DNA tensegrity triangle4. The data demonstrate clearly that it is possible to design and self-assemble a well-ordered macromolecular 3D crystalline lattice with precise control.