Design, Synthesis and Applications of Biologically Inspired Nanomaterials

Previous work in the field of membrane biology resulted in the development of the lipidic cubic phase (LCP) concept for the crystallization of membrane proteins. LCP-crystallized bacteriorhodopsin (bR) yielded the first high resolution X-ray structure of this proton pump in the ground state. Subsequently, microcrystals of bR were illuminated and intermediates in bR’s photocycle were cryo-trapped, enabling the elucidation of their high-resolution structures, and leading to a molecular view of transmembrane proton pumping. A hypothetical mechanism for the incorporation in, and crystallization from LCPs has been proposed. Membrane proteins are thought to reside in curved lipid bilayers, to diffuse into patches of lower curvature, and to incorporate into lattices which associate to form highly ordered three-dimensional crystals. This mechanism entails a critical role for lipid structure and dynamics in the formation of well-ordered crystals of membrane proteins. Crystallization of numerous other membrane proteins of various sources, size and structure has established the generality of the LCP methodology in membrane biology. Current research in the field aims at the development of further lipidic matrices for functional and structural investigation of membrane proteins.

Current research in the lab builds upon these concepts and insights. In the field of molecular design and synthesis of biologically inspired nanomaterials with novel properties, we have recently synthesized a series of novel lipids with designed functionalities. These lipids are based on conjugation of a-amino acids, their esters, cationic, anionic, neutral and photochromic moieties to the lipophilic 9-cis octadecenyl chains by amide, ester, thioester or amine bonds. Because of the plasticity and flexibility of the bilayers that comprise LCPs, we envision that these lipid additives would assemble with monoacylglycerols such as monoolein (MO) to form bicontinuous LCPs. These materials would exhibit the well-known material properties of LCPs such as phase stability, optical transparency and chemical permeability, and in addition would perform as functional materials by design.

In the area of prebiotic chemistry, we have proposed tailored lipidic cubic phase biomaterials comprised of a blend of MO host and an oleolipid-nucleic acid conjugate guest as an alternative semipermeable protocell model. Such molecular systems exhibit base pairing between the lipid-anchored base and complementary oligonucleotides from solution, and were shown to sequester sequence-specific DNA within the modified LCP. The use of a lipid polymorph that is stable in bulk water over a large temperature range highlights this protocell model in contrast to the use of metastable micelle and vesicular models.

Work in the field of drug delivery, biosensors and biofuel cells is highly interdisciplinary. The drug delivery systems under investigation should be robust and stable, with a potential of high spatial and temporal control of the delivery process. Biosensors and biofuel cells under consideration aim at harvesting membrane proteins for the desired functions.