A computational model for the isothermal assembly of tiled DNA nanostructures

Abstract

Complex DNA nanostructures have proven difficult to assemble from starting materials. Inefficient nanostructure assembly constitutes a barrier to the widespread use of DNA nanotechnology and is difficult to investigate experimentally due to the complicated nature of the assembly. This work introduces a type of tile assembly model, the isothermal tile assembly model (iTAM). The iTAM seeks to capture the behavior of assembling DNA tile nanostructures to identify design factors and reaction conditions which improve assembly yields. Simulations using the iTAM model explain the experimental observation that only a narrow range of temperatures permit optimal isothermal assembly of tile-based DNA nanostructures. This narrow temperature range reflects a balance between the stabilization of non-designed interactions at low temperatures and the destabilization of the overall designed structure at high temperature. Simulations based on the iTAM are effective at estimating the temperature of optimal assembly unique to 25 two-dimensional tile designs, with an mean error of estimation of 4.6 degrees C. Results from the iTAM indicate that optimal assembly temperatures are determined largely by the strength of tile-tile domain interactions. For a given tile design, tile concentration and the length of time represent convenient axes of control over tile assembly. Kinetic trapping that blocks complete assembly of a tile design is likely to be overcome by increasing the both temperature and tile concentration in the assembly reaction. Such a change also substantially decreases the computationally predicted time required for complete assembly.