Cells synthesize and modify lipids through complex metabolic pathways, requiring numerous enzymes and synthetic steps. To study the behavior of specific lipids in model and live cell systems it would be beneficial to create tools for simple and selective lipid synthesis which are compatible with biological conditions. Recently, we have developed platforms for chemoselective synthesis and modification of biomimetic lipids using non-membrane forming precursors. These tools allow for the in-situ synthesis and assembly of lipid membranes as well as their modification through fatty acyl exchange and head group modification. Using these techniques, we have demonstrated the successful lipid tail remodeling of synthetic membranes leading to micron-sized microdomain formation, and the modulation of membrane charge, triggering the association and curvature inducing activity of the protein amphiphysin. Additionally, we have synthesized a new class of biorthogonal “lipid-anchors” which allow for the selective and controlled localization of proteins of interest to both synthetic and live-cell membranes. These lipids utilize a benzylguanine moiety conjugated to the phospholipid head group. This substrate reacts selectively with the protein SNAP-tag, allowing for recruitment of SNAP-tag fusion proteins to the membrane surface. Using SNAP-tag lipid-anchors, we have demonstrated selective protein tethering in phospholipid vesicles, E. coli lysate containing model cells and the surface of live mammalian cells.

Chemoselective assembly and modification of lipids for use in model and live-cell systems

254th National Meeting (2017)

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