DNA Droplets: Intelligent, Dynamic Fluid

Abstract

Figure 1. Overview of DNA droplets as a hybrid from DNA nanotechnology and liquid-liquid phase separation (LLPS) studies. A) DNA droplets, micro-scale condensates of DNA nanostructures (DNA motifs) self-assembled via sticky ends (SEs). A Y-shaped DNA motif (Y-motif) is a branched nanostructure of three single-stranded DNAs (ssDNAs) hybridized to form the branching stems. At the end of each branch, a single-stranded SE protrudes. Two basic features are highlighted: (i) Programmable interactions. DNA droplets favor sequence-specifically selective interactions as encoded in the SE sequences. (ii) Programmability in mechanical properties.The number of the SEs in a single DNA motif, serving as the valency, can be designed to determine the macroscopic rheological properties, including diffusion coefficient and viscoelastic behavior. Adapted with permission. [29]

DNA droplets for intelligent and dynamical artificial cells: from the viewpoint of computation and non-equilibrium systems

“…Because of the reversible and weak bonds, LLPS droplets have dynamical properties that change their state and function in response to the environment, including temperature, pH, ionic strength and biomolecules. Similarly, DNAbased physical gels also have the property of shifting their structure from a gel state to a liquid-like state by responding to the environment thanks to the reversible binding (figure 4a) [20,21,64,[66][67][68][69].…”

“…The physical properties of DNA droplets based on branched nanostructures, such as their stability and specificity, are controlled not only by the sticky-end sequences of the branched nanostructures but also by nanomechanical and physico-chemical properties of DNA nanostructures, such as the number of branches; the shape, size and flexibility of the nanostructures; and amphiphilicity of the chemically modified DNA nanostructures [21,64,65,67,70,[75][76][77][78]. For example, if the number of branches changed from 3 to 6 arms, the gel-droplet transition temperature rose about royalsocietypublishing.org/journal/rsfs Interface Focus 13: 20230021 30°C in the case of the 8-nucleotide sticky end [21].…”

Amphiphiles Formed from Synthetic DNA-Nanomotifs Mimic the Stepwise Dispersal of Transcriptional Clusters in the Cell Nucleus

“…Conventionally, such compartmentalization is attributed to cellular organelles that are enclosed by membranes. More recently, processes based on liquid–liquid phase separation (LLPS) resulting from transient interactions were implicated in subcellular compartmentalization in biomolecular condensates. − The transfer of biologically inspired compartmentalization via LLPS into biomimetic and synthetic systems yields remarkable design possibilities and performance increase . One example, a recently developed platform for fully programmable, multispecies phase separation is now available via DNA-nanomotifs, whose interactions are based on homology of ”sticky ends” of exposed, self-complementary single-stranded DNA. , This platform has enabled the construction of a synthetic DNA segregation module that mimics chromosome separation during mitosis .…”

Amphiphiles formed from synthetic DNA-nanomotifs mimic the step-wise dispersal of transcriptional clusters in the cell nucleus

“…Here, theoretical concepts from polymer systems are applied to explain selective and dynamic compartmentalization of specific molecular components and functions of biological cells. While much debate remains on LLPS in biological cells [3], the transfer of biologically inspired compartmentalization via LLPS into biomimetic and synthetic systems yields remarkable design possibilities and performance increases [4]. A flexible platform for fully programmable, multi-species phase separation is now available via DNA-nanomotifs, whose interactions are based on homologoy of “sticky ends” of exposed, self-complementary single-stranded DNA [5, 6].…”