Proceedings from the Workshop on Biomedical Materials at the Edge: Challenges in the Convergence of Technologies (2006)

Nadrian C. Seeman

New York University

Structural DNA nanotechnology uses the concept of reciprocal exchange between DNA double helices (hairpins) to produce branched DNA motifs, such as Holliday junctions, or related structures, such as double crossover (DX), triple crossover (TX), paranemic crossover (PX), and DNA parallelogram motifs. At the Seeman Laboratory at New York University, DNA motifs are combined to produce specific structures by means of sticky-ended cohesion or by other interactions, such as PX cohesion. The key strength of sticky-ended cohesion is that it produces predictable adhesion combined with known structure. From branched junctions, researchers at the Seeman Laboratory have constructed DNA stick-polyhedra, whose edges are double helices and whose vertices are the branch points of DNA branched junctions. They have also begun to template the topology of industrial polymers, such as nylon, with DNA-like scaffolds. That living systems have nanoscale structural components proves that autonomous systems can build up and function on this scale; such systems are capable of energy transduction and replication. The overall challenge that biology presents to the physical sciences is to move from biokleptic to biomimetic to abiological systems that perform in this same manner. To move in the direction of nanorobotics, Seeman Laboratory researchers have used two DX molecules to construct a DNA nanomechanical device by linking them with a segment that can be switched between left-handed Z-DNA and right-handed B-DNA. PX DNA has been used to produce a robust sequence-dependent device that changes states by varied hybridization topology. The sequence-dependent nature of this device means that a variety of such devices attached to a motif can all be addressed individually. Two such devices have been coupled to create a prototype of a translational machine, logically equivalent to a ribosome. Researchers have used sequence control to build a bipedal walker that moves on a sidewalk. They have also constructed a protein-activated device that can be used to measure the ability of the protein to do work.

Virgil Percec

University of Pennsylvania

The fluid mosaic model of a cell membrane can be used as a model for the design of multifunctional, porous, supramolecular systems. It is possible to understand the functioning of molecules by looking at their structure. Porous transmembrane proteins can be either nonselective or selective, with all selective protein channels being hydrophobic. The Percec group is working to develop synthetic supramolecular porous structures. The group has developed a library of synthetic building blocks that includes combinations of macrocyclic, dendritic, and other primary sequences that are able to fold into well-defined conformations and also contain all the information required to control and self-repair their secondary, tertiary, and quaternary structure at the same level of precision as in biological molecules. Synthetic peptides can self-assemble to form porous and nonporous protein mimics, enabling the design of helical porous protein mimics. Protein translocation can be achieved through dendritic dipeptide hydrophobic pores.

James L. Harden

Johns Hopkins University

In recent years, genetically engineered proteins have emerged as novel and potentially useful components for biomaterials. Engineered proteins are particularly attractive as building blocks for biomaterials because they are natural constituents of the body. Their tremendous potential derives from the sequence diversity possible in polypeptide systems and researchers’ ability to use the tools of molecular biology and biochemistry to design and produce engineered proteins with a precisely controlled sequence. Precise control of sequence allows for control of the secondary and tertiary structure of these proteins, inclusion and presentation of bioactive polypeptides (such as ligands for cell surface receptors), and the directed assembly of these proteins at interfaces or into three-dimensional structures. In this presentation, several case studies of proteins engineered for biomaterials applications are described. These case studies are then used to highlight the strengths and challenges of the protein engineering approach and the potential for these systems in hybrid biomaterials platforms.