Sequential Activation of Spatially Localized Oligonucleotides

Abstract

The programmable spatiotemporal activation of molecules could be used to create stimuli-responsive biomaterials capable of executing multistage sensing and computational processes. Here we develop a method for the activation of different DNA molecules in precisely specified locations and times within hydrogels. The activation locations are determined by patterning molecules to be released in their inactive form within hydrogels at resolutions of tens of microns, whereas the time of activation is controlled by a DNA strand displacement reaction cascade that releases the target DNA oligonucleotides at precisely specified time intervals. This programmed activation of DNA from hydrogel substrates thus enables the scalable development of DNA-based reaction-diffusion systems that regulate DNA strand availability in space and time. This system could be used as a platform to autonomously activate predefined chemical signals embedded within a soft material.

Multi-domain automated patterning of DNA-functionalized hydrogels

“…MAPDH could be used to help fabricate multi-domain DNA-functionalized hydrogels capable of complex shape change [42]. Due to the precise control of size, location, and shape of the hydrogels, we envision that MAPDH could be used for local sequestration and release of molecules within hydrogels, either via timed release or designed reactions [6], to direct cell growth [43] or for local self-assembly [44]. Harnessing the biocompatibility and permeability of hydrogels, MAPDH may also be promising in various biomedical applications, such as designing controlled drug delivery systems [18], scaffolds [45], or organ-on-a-chip devices for tissue engineering [46].…”

“…Molecular programs can also be localized, i.e., specific molecules can be anchored in place and interact with diffusing molecules to produce spatiotemporal molecular programs. Spatiotemporal molecular programs can sequentially release DNA at prescribed times and locations, and they can generate stable chemical gradients within a microfluidic chamber [4][5][6]. The DNA molecules that specify a spatiotemporal program can be conjugated to substrates such as hydrogels, surfaces, colloids, cell surfaces, or proteinosomes [3,[7][8][9][10][11].…”