Growth and site-specific organization of micron-scale biomolecular devices on living mammalian cells

Sisi Jia,Yizeng Li,Siew Cheng Phua,Yi Li,Abdul M Mohammed,Michael Pacella,Yuta Nihongaki,Takanari Inoue,Sean Sun,Rebecca Schulman

doi:10.1038/s41467-021-25890-z

Abstract

Mesoscale molecular assemblies on the cell surface, such as cilia and filopodia, integrate information, control transport and amplify signals. Designer cell-surface assemblies could control these cellular functions. Such assemblies could be constructed from synthetic components ex vivo, making it possible to form such structures using modern nanoscale self-assembly and fabrication techniques, and then oriented on the cell surface. Here we integrate synthetic devices, micron-scale DNA nanotubes, with mammalian cells by anchoring them by their ends to specific cell surface receptors. These filaments can measure shear stresses between 0-2 dyn/cm2, a regime important for cell signaling. Nanotubes can also grow while anchored to cells, thus acting as dynamic cell components. This approach to cell surface engineering, in which synthetic biomolecular assemblies are organized with existing cellular architecture, could make it possible to build new types of sensors, machines and scaffolds that can interface with, control and measure properties of cells.

Highlights

Mesoscale molecular assemblies on the cell surface, such as cilia and filopodia, integrate information, control transport and amplify signals
We develop a method in which a DNA nanotube seed serves as an anchor and presents numerous binding sites that attach quickly and effectively irreversibly to the desired receptor
We measured the rate of DNA nanotube seed/cell interaction by adding Atto488-labeled DNA nanotube seeds to HeLa cells in culture (Supplementary Note S5)

Summary

Introduction

Mesoscale molecular assemblies on the cell surface, such as cilia and filopodia, integrate information, control transport and amplify signals. We integrate synthetic devices, micron-scale DNA nanotubes, with mammalian cells by anchoring them by their ends to specific cell surface receptors These filaments can measure shear stresses between 0-2 dyn/cm[2], a regime important for cell signaling. Nanotubes can grow while anchored to cells, acting as dynamic cell components This approach to cell surface engineering, in which synthetic biomolecular assemblies are organized with existing cellular architecture, could make it possible to build new types of sensors, machines and scaffolds that can interface with, control and measure properties of cells. Assembling synthetic micron-scale cell structures and controlling their dynamics are key goals of synthetic biology and nanotechnology[6] because these abilities could make it possible to construct, for example, new cellular reaction chambers, sensors, and information and material conduits. While controlling interactions between cell receptors and nanostructures has been studied in the context of therapeutic modulation of receptor activity[14,15] and for directing import of therapeutics[16,17,18,19], less is known about creating and organizing microstructures that programmatically modify and extend cell surface architecture[7,20,21,22]

Methods

Results

Conclusion