Activatable Tiles: Compact, Robust Programmable Assembly and Other Applications

Abstract

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 (i) a single "activated" tile with output pads that can bind with other tiles, along with (ii) 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. * This paper is a revised version of the conference proceedings extended abstract: Urmi Majumder, Thomas H. 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 (i) a novel system for concentration of molecules, and (ii) a catalyst in sequentially triggered chemical reactions.

Simulating Self-replicating Patterns of DNA Tiles

“…Thus, any effort to reduce the error rate (ε) by tuning physical parameters (Gmc and Gse) would result in a quadratic reduction of the growth rate. Error reduction without significant fall off in assembly growth rate could be achieved using redundant tile sets [20,7] or by protecting tile's inputs and outputs [4,10,6]. …”

Meta-DNA: synthetic biology via DNA nanostructures and hybridization reactions

“…While TAM is geared towards studying the computational power of self-assembly (see [13][14][15][16][17][18][19][20]), our tile-based model is used to represent the dynamic assembly processes and state changes that occur in mDNA reactions. We model a meta-nucleotide as an activatable tile [21] having three activatable pads: a 5 0 pad, a 3 0 pad and a base pad and represent it by a square tile as illustrated in figure 1a. The tile has directionality as indicated by an arrow from 5 0 to 3 0 which is imposed by the sequence in which the pads are activated, with 5 0 always activated before 3 0 .…”

Isothermal reactivating Whiplash PCR for locally programmable molecular computation

“…However, to the best of our knowledge, there exists no WPCR protocol that is both isothermal and autocatalytic and capable of preventing back-hybridization simultaneously. Our isothermal and reactivating protocol is partially inspired by our previous work where we used a combination of DNA polymerization and strand displacement events to minimize errors in computational tile assembly (Majumder et al 2008).…”