Self-Assembly of DNA into Nanoscale Three-Dimensional Shapes

William Shih, Assistant Professor of Biological Chemistry and Molecular Pharmacology, Harvard Medical School

I will present a general method for solving a key challenge for nanotechnology: programmable self-assembly of complex, three-dimensional nanostructures. Previously, scaffolded DNA origami had been used to build arbitrary flat shapes 100 nm in diameter and almost twice the mass of a ribosome. We have succeeded in building custom three-dimensional structures that can be conceived as stacks of nearly flat layers of DNA. Successful extension from two-dimensions to three-dimensions in this way depended critically on calibration of folding conditions. We also have explored how targeted insertions and deletions of base pairs can cause our DNA bundles to develop twist of either handedness or to curve. The degree of curvature could be quantitatively controlled, and a radius of curvature as tight as 6 nanometers was achieved. This general capability for building complex, three-dimensional nanostructures will pave the way for the manufacture of sophisticated devices bearing features on the nanometer scale.

Companion Tutorial: 
October 6, 2009
How to Design Pre-stress into DNA Nanostructures
10:30 am
153 Noyes

I will discuss in greater detail how global twist and curvature can be implemented in DNA nanostructures via targeted deletions and insertions of base pairs using simple calculations along with caDNAno, an open-source package with an easy-to-use graphical interface that enables rapid prototyping of 2D and 3D DNA-origami nanostructures (available for free download at http://cadnano.org/). The observed global twist of 3D DNA origami with helices arranged on honeycomb versus square lattices will be compared and contrasted. Next I will describe a second class of pre-stressed DNA nanostructures: Kenneth-Snelson–inspired "floating compressions" in which single strands of DNA act by entropic coiling as tensional wires that connect rigid double-stranded DNA bundles acting as compression-bearing struts. Finally I will discuss research directions for scaling DNA origami to construction of increasingly large and complex nanostructures, including the employment of scaffolds fed to the folding reaction in the form of double-stranded DNA.