Seminar

Compartmentalization is a defining feature of all forms of life. Numerous processes like signaling, transport, and biosynthesis take place in cells through the interplay between structure and dynamics of cellular membranes. Amphiphilic lipid molecules are the primary building blocks of cellular membrane compartments. Here we take a bottom-up approach to develop a fundamental understanding of cellular processes involving lipid membranes. Various lipid architectures were used to build functional models (artificial cells and organelles) of the membranous structures found in cells. We utilized giant vesicles to recapitulate the basic membrane-bound structure of cells. To model membrane-rich organelles such as the endoplasmic reticulum, we described a novel bicontinuous lipid sponge phase lipid droplet system. With their nanoporous structure consisting of an interconnected network of bilayers, lipid sponge droplets can sequester hydrophobic and hydrophilic molecules in a programmable manner at concentrations comparable to that in cells. The droplets can further sequester and release proteins rapidly and reversibly to control enzymatic reactions in response to external stimuli such as light. Next, to understand the origins of cellular compartmentalization, we explored various minimal chemoenzymatic pathways for de novo generation of lipid membranes. We demonstrated a few primitive modes of growth and division of such membrane compartments to provide a hint at how earliest cells may have proliferated. Given their central role in cellular physiology, lipid membranes are also key to understanding the fundamentals of many infectious diseases. For example, pathogens like viruses hijack the dynamical processes of the cellular membrane systems to gain entry. We describe the application of surface-immobilized lipid vesicles mimicking endosomes to model the events concerning cellular attachment, endosomal membrane fusion, and genome transfer of enveloped viruses such as influenza. Overall, bottom-up construction of artificial cells and organelles is a highly creative pursuit which leads to the discovery of new novel functional materials, emergent phenomena, and research tools.