Webinar

Amphiphilic lipid molecules are the primary building blocks of biological membranes in all domains of life. Numerous cellular processes like signaling, transport, and biosynthesis take place through the interplay between structure and dynamics of lipid molecules. Here I describe miscellaneous studies on self-assembled lipidic structures to understand the importance of compartmentalization in bottom-up artificial systems and also in biological organisms.

In the first part, I discuss the diverse self-assembled structures formed by the synthetic single-chain non-ionic lipid galactose oleoyl amide (GOA). GOA forms vesicles in water which undergo temperature-dependent reversible transformation to fibers. In the presence of Triton-X class detergents, GOA forms sponge phase droplets robustly. With their nanoporous structure consisting of an interconnected network of bilayers, lipid sponge droplets were described as mimics of membrane-rich organelles like the endoplasmic reticulum. The droplets can spontaneously partition membrane proteins in functional form. Furthermore, the droplets can be smartly programmed to sequester and release proteins rapidly and reversibly to control enzymatic reactions in response to external stimuli such as light.

In the second part, I describe the structure-function relationships in glycerol dialkyl glycerol tetraethers (GDGTs) – an enigmatic class of bipolar lipids found only in the domain Archaea. Given their supposed membrane-spanning (i.e. monolayer-forming) nature, it is unclear how GDGT membranes undergo fundamental processes such as fusion which require a bilayer structure. Building on structural studies, I show that the GDGT lipids have the conformational flexibility to fold into U-shapes and therefore form bilayer domains in the membranes which act as the sites of membrane fusion.

In the third part, I will briefly describe the discovery of a novel form of the eukaryotic lipid sphingomyelin synthesized through a metal-catalyzed esterification reaction under biochemically relevant conditions.

Finally, I will offer future directions regarding development of novel lipid-based tools for membrane protein reconstitution and little explored problems on membrane biophysics of viruses.