Programming Cell–Cell Communications with Engineered Cell Origami Clusters

Abstract

Cells existing in the form of clusters often exhibit distinct physiological functions from their monodispersed forms, which have a close association with tissue and organ development, immunoresponses, and cancer metastasis. Nevertheless, the ability to construct artificial cell clusters as in vitro models for probing and manipulating intercellular communications remains limited. Here we design DNA origami nanostructure (DON)-based biomimetic membrane channels to organize cell origami clusters (COCs) with controlled geometric configuration and cell–cell communications. We demonstrate that programmable patterning of homotypic and heterotypic COCs with different configurations can result in three distinct types of intercellular communications: gap junctions, tunneling nanotubes, and immune/tumor cell interactions. In particular, the organization of T cells and cancer cells with a prescribed ratio and geometry can program in vitro immunoresponses, providing a new route to understanding and engineering cancer immunotherapy.

DNA nanostructure-based nucleic acid probes: construction and biological applications

“…However, the assembly of cells in a spatial orientation remains to be explored. Fan et al 127 reported a DNA origami nanostructure to assemble homogeneous and heterotypic cells in 3D space ( Fig. 9B ).…”

Synthetic DNA for Cell‐Surface Engineering

“…Although this method needs a large number of DNA oligonucleotides, the self‐assembly happens in one single mixing step. With the DNA origami method, DNA nanostructures with different shapes such as DNA “breadboards”, DNA “nanocalipers”, and DNA “nanobundles” have been developed [41d–h] . As these DNA nanostructures can be functionalized with aptamers, peptides, antibodies, or lipids for cell recognition, they can be anchored on the cell membrane for surface engineering.…”

“…As each “breadboard” has multiple oligonucleotides, it enables programmed assembly of biomolecules on the cell surface. Similarly, DNA tetrahedron and Janus DNA nanostructures have been anchored on cell surfaces through polyvalent interactions for directing cell–cell adhesion [41a,f] . Surface engineering with DNA was also applied to build cell–hydrogel constructs that hold potential for applications such as tissue engineering and cell separation [37b, 48] .…”

“…The promotion of cell–cell recognition may also be useful for tissue engineering. Complementary DNA strands engineered on the cell surface can be used as a synthetic ligand and receptor pair to direct cell aggregation for the formation of microtissues [18b, 20c, 34, 41a,e,f] . The Bertozzi group applied the monovalent engineering method to functionalize Chinese hamster ovary (CHO) and hematopoietic progenitor cells with complementary DNA strands [18b] .…”

Functional Immunostimulating DNA Materials: The Rising Stars for Cancer Immunotherapy

“…has successfully built cell‐origami clusters (COCs) with DNA origami nanostructures and realized precise spatial arrangements of immune cells and tumor cells (Figure 5D). [ 76 ] In their work, they constructed a six‐helix bundle DNA origami nanostructure as the platform with single‐stranded DNA overhangs extended from the edges. Cells were surface modified with complementary DNA strands to those overhangs and cell clusters formed through DNA hybridization reactions.…”