Understanding Membranes through the Molecular Design of Lipids

Abstract

Lipids are amphiphilic molecules that are composed of hydrophilic and hydrophobic regions. A typical membranous aggregate (vesicles, water-filled lipid nanospheres) is formed upon the self-organization of lipids in water from a diverse collection of amphiphiles producing a dynamic supramolecular structure that shows phase behavior and ordering as required for specific biological functions. The determination of various physical properties of lipid aggregates is the key to determining structure−function relationships. Over the years, we have designed and synthesized a wide variety of lipid molecular systems for the investigation of their membrane-forming properties and have used them for purposes such as gene delivery and enzyme activation. In this feature article, we focus on our work on various types of lipids including ion-paired amphiphiles, cholesterol-based lipids, aromatic lipids, macrocyclic lipids containing disulfide tethers, cationic dimeric lipids, and so forth. The emphasis is on experimental design and bottom-line conclusions.

Synthesis of phospholipids on a glyceric acid scaffold: design and preparation of phospholipase A2 specific substrates

“…Anal. Cald for C 38 H 50 O 9 S• 1 / 12 C 6 H 6 : C, 67.08; H, 7.38; Found: C, 67.07; H, 7.42; MS MNa + C 38 H 50 O 9 SNa Calcd: 705.3073, Found: 705.3100.…”

“…1 The compounds are needed for structural and dynamic studies of biomembranes and membrane-bound enzymes with particular emphasis on establishing structure-activity relationships with respect to phospholipid-phospholipid and phospholipid-protein interactions, as well as for mechanistic elucidation of phospholipid metabolizing enzymes 1–3 . Specifically, phospholipases A 2 (PLA 2 s) comprise a large group of intracellular and secreted enzymes that catalyze the hydrolysis of the sn -2-ester bond of glycerophospholipids (Figure 1), yielding fatty acids such as arachidonic acid, and lysophospholipids.…”

Unusual triskelion patterns and dye-labelled GUVs: consequences of the interaction of cholesterol-containing linear-hyperbranched block copolymers with phospholipids

“…[1][2][3][4] Cholesterol is one of the most abundant molecules in biological membranes (4 to 50 mol%). Phospholipids consist of a hydrophilic head group, which is zwitterionic in the case of phosphatidylcholines, and a hydrophobic tail with two fatty acyl chains.…”

Understanding the photothermal heating effect in non-lamellar liquid crystalline systems, and the design of new mixed lipid systems for photothermal on-demand drug delivery

“…43 However, as the global packing constraints required for reverse phase formation can also be achieved using lipid mixtures, 44 the second part of this research describes investigation of combinations of readily available lipids which have the potential to display a lamellar to non-lamellar liquid crystalline nanostructure transition in response to moderate temperature changes. 43 However, as the global packing constraints required for reverse phase formation can also be achieved using lipid mixtures, 44 the second part of this research describes investigation of combinations of readily available lipids which have the potential to display a lamellar to non-lamellar liquid crystalline nanostructure transition in response to moderate temperature changes.…”