In multicellular organisms, cell–cell communication was mainly mediated by membrane receptors. The development of artificial receptors to monitor and control intercellular reactions would be highly desired. Cell membrane-anchored DNA platforms, with high programmability and flexibility, showed great promise in mimicry and manipulation of cellular interaction.
Based on DNA hybridization with predictable thermodynamics, Zhao et al. reported DNA tension probes for quantifying the tensile forces at the junction between cells. As shown in
Figure 1A,B, the tension probe was inset into the cellular junction through both the hydrophobic interaction and the ligand–receptor interaction
[1]. Upon sensing the intercellular tension force, the DNA probe would undergo a conformation switch to separate the fluorophore pair, thus allowing dynamic detection of the intercellular force via FRET. Moreover, the capability to modulate the intercellular reaction would offer us a straightforward strategy for analyzing related biological processes. Xiong et al. mimicked the natural cell–cell adhesion by modifying the cell surface with specific aptamers (
Figure 1C,D)
[2]. Based on the aptamer-mediated molecular recognition, the effector T cells could specifically bind with target cancer cells, resulting in enhanced cancer-killing efficacy. To achieve intelligent control over the cellular interaction, DNA-based Boolean logic operation was utilized
[3]. Li et al. engineered an amphiphilic DNA tetrahedral construct on the cell surface, which could undergo a conformation switch and assemble functional modules for sensing the cell’s adaptive response to the external environment
[4]. As such, this membrane-anchored DNA construct allowed regulation of the cellular interaction coordinated with the cellular activity.
Another application for membrane anchored-DNA probes was to manipulate the morphology of cells with spatial resolution. The cell growth could be controlled via hybridization of the membrane-anchored DNA with the complementary DNA on the substrate interface
[6]. Meanwhile, a 3D cell microsphere could be constructed by stepwise and programmable cell assembling, which displayed great promise for the construction of 3D artificial tissues
[7]. In addition to single-stranded DNA probes, DNA nanostructures provided versatile tools for controllable cell assembly
[8]. For example, the assembly between stem cells and niche cells was mediated through the mechanical and morphogen signaling from niche cells, providing a versatile strategy for the generation of stem cells in vitro
[4].