Activatable tiles for compact robust programmable molecular assembly and other applications

作者：Majumder Urmi; Garg Sudhanshu; LaBean Thomas H; Reif John H^*

来源：Natural Computing, 2016, 15(4): 611-634.

DOI：10.1007/s11047-015-9532-3

• DNA self-assembly
• Error correction
• Tile assembly model
• Strand displacement
• Programmable molecular machines
• Deprotection systems
• Concentration systems
• Reaction catalyzation

Algorithmic DNA self-assembly is capable of forming complex patterns and shapes, that have been shown theoretically, and experimentally. Its experimental demonstrations, although improving over recent years, have been limited by significant assembly errors. Since 2003 there have been several designs of error-resilient tile sets but all of these existing error-resilient tile systems assumed directional growth of the tiling assembly. This is a very strong assumption because experiments show that tile self-assembly does not necessarily behave in such a fashion, since they may also grow in the reverse of the intended direction. The assumption of directional growth of the tiling assembly also underlies the growth model in theoretical assembly models such as the TAM. What is needed is a means for enforce this directionality constraint, which will allow us to reduce assembly errors. In this paper we describe a protection/deprotection strategy to strictly enforce the direction of tiling assembly growth so that the assembly process is robust against errors. Initially, we start with (1) a single "activated" tile with output pads that can bind with other tiles, along with (2) a set of "deactivated" tiles, meaning that the tile's output pads are protected and cannot bind with other tiles. After other tiles bind to a "deactivated" tile's input pads, the tile transitions to an active state and its output pads are exposed, allowing further growth. When these are activated in a desired order, we can enforce a directional assembly at the same scale as the original one. Such a system can be built with minimal modifications of existing DNA tile nanostructures. We propose a new type of tiles called activatable tiles and its role in compact proofreading. Activatable tiles can be thought of as a particular case of the more recent signal tile assembly model, where signals transmit binding/unbinding instructions across tiles on binding to one or more input sites. We describe abstract and kinetic models of activatable tile assembly and show that the error rate can be decreased significantly with respect to Winfree's original kinetic tile assembly model without considerable decrease in assembly growth speed. We prove that an activatable tile set is an instance of a compact, error-resilient and self-healing tile-set. We describe a DNA design of activatable tiles and a mechanism of deprotection using DNA polymerization and strand displacement. We also perform detailed stepwise simulations using a DNA Tile simulator Xgrow, and show that the activatable tiles mechanism can reduce error rates in self assembly. We conclude with a brief discussion on some applications of activatable tiles beyond computational tiling, both as (1) a novel system for concentration of molecules, and (2) a catalyst in sequentially triggered chemical reactions .

• 出版日期2016-12