UC San Diego

How life emerged is a mystery, but theories have advanced remarkably in the last century. Research has traced current molecular structures back to an ancient period in life when RNA assumed a dominant role. A second line of research has explored ways to synthesize biological molecules from simpler molecules thought to exist on the nascent Earth. The first approach can only trace life back to the last universal common ancestor, while the second approach has not yet demonstrated that simple biological molecules can interact in life-like ways. The results communicated in this dissertation provide an example of a complex molecular system that could help fill in the gap between these two disparate domains. Though our results are not expected to bear much resemblance to the actual molecules that first gave rise to life, the artificial system presented here has some striking similarities to living systems and may have fundamental processes in common with the ancient molecular assemblies that gave rise to the first life forms. It is also the most complex example to date of a self-propagating molecular network resembling life.

In the first study of the dissertation we report on a novel lipid-based system that harnesses autocatalysis to drive continual membrane growth. Lipid membranes are ubiquitous in all domains of life; like living systems, lipid assemblies assume complex macromolecular structures and non-equilibrium states. Previous studies have exploited these properties to drive physical processes (vesicle growth and/or division) by adding additional lipids in the form of micelles or feeder vesicles. A smaller number of studies have added complexity by using catalysts to generate additional lipids through catabolic reactions, which subsequently drive vesicle growth. Such systems, however, are unable to sustain persistent phospholipid production. Here we couple a hydrophobic autocatalyst to lipid membranes and lipid membrane production, resulting in an anabolic metabolism that continually resupplies all of the components needed to form additional catalytic membranes. A remarkable consequence of the coupled anabolic reactions is the apparent ability of the catalytic membranes to selectively take up precursors and synthesize modified catalytic membranes under different environmental conditions.

In the second study of the dissertation we report on the design and creation of a ruthenium photoredox trigger that induces electron transfer, upon excitation with visible wavelengths, and drives biomimetic phospholipid synthesis. All known living systems couple free energy both to electron transport chains in membrane bilayers and to anabolic reactions. Light harvesting systems fundamentally changed the surface of the Earth; here we demonstrate the first instance of coupling a light-harvesting electron transport chain to an anabolic reaction that drives membrane synthesis.