DNA-based Artificial Mimics of Cell-surface Machinery

Abstract

The plasma membrane of cells has evolved to mediate a broad array of functionalities critical to life, such as molecular trafficking, signal transduction, motility, adhesion and communication. These functionalities are often reliant on highly sophisticated membrane-anchored nano-machines, and enabled by the ability of the cell to regulate their spatio-temporal distribution and interactions.

Bottom-up synthetic biology aspires to replicate the rich phenomenology associated with biological systems in artificial cells, micron-sized entities created de-novo to display life-like behaviours. Artificial cells have been constructed using a range of elementary molecular components, from lipids to polymers and proteins, yet artificial cellular membranes are usually passive enclosures lacking the diverse functionalities hosted by their biological counterparts.

DNA nanotechnology has emerged as a prime route for biomimicry given its yet unparalleled control over the structure and dynamic responses of synthetic nanostructures. Particularly promising in the context of bottom-up synthetic biology is the possibility of constructing bio-inspired DNA devices that mimic the structure and action of membrane-bound biological machines, and integrate them with artificial-cell membranes to unlock some of the rich functionalities sustained by the plasma membrane.

In this thesis, I explore the use of functional DNA nanostructures to program the properties and responses of the lipid membranes of synthetic cells. By depending our understanding of how cations, hydrophobic modifications of the nanostructures, and bilayer-phase influence DNA-lipid interactions, I was able to emulate key phenomena exhibited by biological interfaces, such as surface patterning, cargo transport, and lipid domain sculpting. In addition, I show how membrane phase transitions enable reshuffling the content of proto-cells, leading to the assembly of functional nucleic acids in daughter proto-cells. Altogether, my findings showcase the potential that DNA-membrane platforms have for biomimicry, unlocking pathways for engineering ever-more intricate functionalities that will help artificial cells realise their paradigm-shifting potential.