Joshua Lequieu

The ability to engineer the self-assembly of nano-scale objects to create highly ordered materials is of considerable scientific and practical interest. This new class of materials represents a powerful approach for engineering the next generation of devices whose mechanical, optical, and electrical properties can be precisely tuned at the molecular scale. Though significant strides toward this goal have been achieved in recent years, the complexity achieved in engineered systems is still far surpassed by that achieved by nature. Precise self-assembly is achieved by nature through proteins and nucleic acids that fold into intricate, three-dimensional, and importantly, functional structures. A promising avenue toward improved engineered systems is to draw on discoveries from biophysics in order to inspire new approaches and paradigms for self-assembly and materials design. In Joshua's research, he explores the interplay between biophysics and engineering by exploring the self-assembly of DNA.

Joshua's PhD research began at the smallest length scales of DNA, first by understanding the hybridization of DNA, and then how hybridization can be used in materials to direct the self-assembly of gold nanoparticles. He presented the first evidence of a tunable mechanical response in these assemblies, thereby suggesting the possibility of mechanical meta-materials constructed using DNA. His research then proceeded to larger length scales, where he examined the biophysical processes that control the compaction of DNA into chromatin. Using a detailed molecular model, he explored the free energies and dynamics of the smallest building block of chromatin, a protein-DNA complex called the nucleosome. These results are in quantitative agreement with existing experimental measurements, and help to explain the molecular factors that dictate the first stages of DNA compaction into chromatin. Lastly, he designed a multi-scale approach that can couple information across different length scales of chromatin in order to examine the folding of large regions of DNA. By drawing on both the biophysics and engineering literature, his research suggests new approaches for materials design and offers new paradigms for synthetic systems that seek to mimic the complexity achieved by nature.