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Applications of Lipid Assemblies in Artificial Cell Development


It is of great fundamental interest to develop experimental model systems to reconstruct design principles underlying formation of living cells and shed light on how life emerged on Earth and possibly elsewhere. An ambitious strategy is the bottom-up approach, which aims to systematically control the assembly of basic building blocks with defined functionality to construct a life-like entity. This dissertation will explore the roles of miscellaneous lipid assemblies as building blocks of artificial cellular compartments.

The first part (Chapters 2 and 3) of this dissertation shows how lipid environments facilitate chemoselective reactions between amphiphilic partners through physical partitioning. Through examples of histidine ligation, and acyl phosphate chemistry we show functionalized micelle-forming amphiphiles react to form amidophospholipids which self-assemble into micron-sized vesicles.

The second part (Chapter 3) of the dissertation seeks to understand the origins of cellular phospholipid synthesis pathways by repurposing soluble fatty acid activating enzymes (fatty acyl adenylate ligase and fatty acyl CoA ligase) to synthesize phospholipids. Such simplified biochemical pathways may provide a hint at how lipids were likely synthesized in a minimal protocell without the necessity of transmembrane protein enzymes.

The third part (Chapters 4 and 5) of the dissertation discusses the vesicle formation from a novel class of single-chain amphiphiles derived from galactopyranosyl head groups and unsaturated fatty acid tails. The geometric parameters and thermodynamic properties of these amphiphilic assemblies are characterized by a host of physical techniques. The vesicles are further shown to sustain model biochemical reactions.

The final part (Chapters 6) of the dissertation describes the formation of sponge phase droplets from fatty acyl galactopyranosylamides and non-ionic detergents. The droplets contain a dense bicontinuous network of bilayers and nanometric aqueous channels, which facilitates molecules to partition into them based on their size, polarity, and specific binding motifs. The sequestration of biomolecules can be programmed by doping the droplets with suitably functionalized amphiphiles. The droplets can harbor functional soluble and transmembrane proteins, allowing for the co-localization and concentration of enzymes and substrates to enhance reaction rates. Droplets protect bound proteins from proteases, and these interactions can be engineered to be reversible and optically controlled.

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