Abstract:Bottom-up synthetic biology aims to construct mimics of cellular structure and behaviour known as artificial cells from a small number of molecular components. The development of this nascent field has coupled new insights in molecular biology with large translational potential for application in fields such as drug delivery and biosensing. Multiple approaches have been applied to create cell mimics, with many efforts focusing on phospholipid-based systems. This mini-review focuses on different approaches to i… Show more
“…Multi‐compartmentalized liposome or polymerosome formulations have indeed been in the focus of biomedical investigations for improved drug and gene delivery as well as biosensing. [ 62–64 ]…”
Membrane enclosed intracellular compartments have been exclusively associated with the eukaryotes, represented by the highly compartmentalized last eukaryotic common ancestor. Recent evidence showing the presence of membranous compartments with specific functions in archaea and bacteria makes it conceivable that the last universal common ancestor and its hypothetical precursor, the protocell, may have exhibited compartmentalization. To the authors’ knowledge, there are no experimental studies yet that have tested this hypothesis. They report on an autonomous subcompartmentalization mechanism for protocells which results in the transformation of initial subcompartments to daughter protocells. The process is solely determined by the fundamental materials properties and interfacial events, and does not require biological machinery or chemical energy supply. In the light of the authors’ findings, it is proposed that similar events may have taken place under early Earth conditions, leading to the development of compartmentalized cells and potentially, primitive division.
“…Multi‐compartmentalized liposome or polymerosome formulations have indeed been in the focus of biomedical investigations for improved drug and gene delivery as well as biosensing. [ 62–64 ]…”
Membrane enclosed intracellular compartments have been exclusively associated with the eukaryotes, represented by the highly compartmentalized last eukaryotic common ancestor. Recent evidence showing the presence of membranous compartments with specific functions in archaea and bacteria makes it conceivable that the last universal common ancestor and its hypothetical precursor, the protocell, may have exhibited compartmentalization. To the authors’ knowledge, there are no experimental studies yet that have tested this hypothesis. They report on an autonomous subcompartmentalization mechanism for protocells which results in the transformation of initial subcompartments to daughter protocells. The process is solely determined by the fundamental materials properties and interfacial events, and does not require biological machinery or chemical energy supply. In the light of the authors’ findings, it is proposed that similar events may have taken place under early Earth conditions, leading to the development of compartmentalized cells and potentially, primitive division.
“…The eld of bottom-up synthetic biology aims to reconstitute the form, function and behaviour of biological organisms from self-assembled chemical systems. [1][2][3][4][5] To this end, different pathways have been explored to create compartmentalised biomimetic microstructures capable of supporting functions such as chemical synthesis, [6][7][8] environment sensing, 9,10 information transduction 11 and motility. 12 One route involves the use of lipid monolayer-stabilised water-in-oil (w/o) droplets, where contact between two droplets leads to the spontaneous selfassembly of a lipid bilayer at the interface (Fig.…”
“…[16][17][18] Just like their biological counterparts, many artificial-cell designs rely on semi-permeable membranes for their compartmentalization requirements, [19][20][21] which can be constructed from polymers 22 and proteopolymer systems, 23,24 colloids 25,26 and, more often, from synthetic lipid bilayers. 21 However, with some remarkable exceptions [27][28][29][30][31] reviewed in ref., 32 the membranes of artificial cells are often passive enclosures, lacking the complex functionalities of biological interfaces. A precise control over the local molecular makeup of synthetic lipid bilayers is therefore highly desirable, and a necessary stepping stone for the development of ever more sophisticated life-like responses in artificial cells.…”
Cell membranes regulate the distribution of biological machinery between phase-separated lipid domains to facilitate key processes including signalling and transport, which are among the life-like functionalities that bottom-up synthetic biology aims to replicate in artificial-cellular systems.
Here, we introduce a modular approach to program partitioning of amphiphilic DNA nanostructures in co-existing lipid domains. Exploiting the tendency of different hydrophobic "anchors" to enrich different phases, we modulate the lateral distribution of our devices by rationally combining hydrophobes, and by changing nanostructure size and its topology. We demonstrate the functionality of our strategy with a bio-inspired DNA architecture, which dynamically undergoes ligand-induced reconfiguration to mediate cargo transport between domains via lateral re-distribution. Our findings pave the way to next-generation biomimetic platforms for sensing, transduction, and communication in synthetic cellular systems.
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