Structural and functional complexity in synthetic cells from amphiphilic DNA nanostars
type: CreativeWork
description: Chemically and spatially distinct compartments serve to localise and segregate function in biological cells. The most fundamental compartment is the cell itself, being physically delimited from its surroundings *via* the phospholipid cell membrane. Sub-compartments within the cell, known as organelles, may also be membrane-bound or membrane-less. The combination of these structures makes a biological cell internally complex and enables intricate cellular functionality. It follows that those seeking to build synthetic cells would aim to replicate such architectures to incorporate structural and functional complexity into their constructs. The bottom-up approach towards building synthetic cells enables the design of structures with meticulous control over their composition and organisation. Design strategies harness simple physical phenomena and utilise elementary and modular building blocks to generate functional cell mimics. The highly programmable and predictable nature of DNA hybridisation has been exploited to develop DNA nanostructures for use as building blocks, with cholesterol-terminated DNA nanostars being one example. These amphiphilic structures, named C-stars, have been shown to self-assemble through non-specific hydrophobic interactions, forming condensates with long-range order capable of hosting various functionality. In this work, I study the formation of binary condensates from the one-pot anneal of two different populations of C-stars. These binary systems undergo size-induced phase separation, and above a particular threshold of difference in size, form condensates with physically distinct, nested compartments. The systematic study of these condensates yields a simple set of design rules for the robust creation of compartmentalised synthetic cell scaffolds. Small unilamellar vesicles are deposited onto these scaffolds to create a phospholipid membrane mimic, which is characterised to determine its structure and permeability. I conclude by demonstra…
abstract: Chemically and spatially distinct compartments serve to localise and segregate function in biological cells. The most fundamental compartment is the cell itself, being physically delimited from its surroundings *via* the phospholipid cell membrane. Sub-compartments within the cell, known as organelles, may also be membrane-bound or membrane-less. The combination of these structures makes a biological cell internally complex and enables intricate cellular functionality. It follows that those seeking to build synthetic cells would aim to replicate such architectures to incorporate structural and functional complexity into their constructs. The bottom-up approach towards building synthetic cells enables the design of structures with meticulous control over their composition and organisation. Design strategies harness simple physical phenomena and utilise elementary and modular building blocks to generate functional cell mimics. The highly programmable and predictable nature of DNA hybridisation has been exploited to develop DNA nanostructures for use as building blocks, with cholesterol-terminated DNA nanostars being one example. These amphiphilic structures, named C-stars, have been shown to self-assemble through non-specific hydrophobic interactions, forming condensates with long-range order capable of hosting various functionality. In this work, I study the formation of binary condensates from the one-pot anneal of two different populations of C-stars. These binary systems undergo size-induced phase separation, and above a particular threshold of difference in size, form condensates with physically distinct, nested compartments. The systematic study of these condensates yields a simple set of design rules for the robust creation of compartmentalised synthetic cell scaffolds. Small unilamellar vesicles are deposited onto these scaffolds to create a phospholipid membrane mimic, which is characterised to determine its structure and permeability. I conclude by demonstra…
author: Malouf, Layla
language: eng
keywords: condensates, DNA nanotechnology, lipid membrane, liquid-liquid phase separation, LLPS, synthetic cells
license: https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/7588e17b-8f56-4eed-90ee-a8ec9ba9f965/download
license: https://creativecommons.org/licenses/by/4.0/
date published: 2024-06-19
date modified: 2026-07-22T22:24:24Z
provider: Cambridge University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Cambridge

PropertyValue
property ID: DOI
value: 10.17863/CAM.112836