Hybrid lipid-based nanostructures

2014-07-11Biological membranes serve several important roles, such as structural support of cells and organelles, regulation of ionic and molecular transport, barriers to non‐mediated transport, contact between cells within tissues, and accommodation of membrane proteins. Membrane proteins and other vital biomolecules incorporated into the membrane need a lipid membrane to function. Due to importance of lipid bilayers and their vital function in governing many processes in the cell, the development of various models as artificial lipid membranes that can mimic cell membranes has become a subject of great interest. ❧ Using different models of artificial lipid membranes, such as liposomes, planar lipid bilayers and supported or tethered lipid bilayers, we are able to study many biophysical processes in biological membranes. The ability of different molecules to interact with and change the structure of lipid membranes can be also investigated in artificial lipid membranes. An important application of lipid bilayer‐containing interfaces is characterization of novel membrane proteins for high throughput drug screening studies to investigate receptor‐drug interactions and develop biosensor systems. Membrane proteins need a lipid bilayer environment to preserve their stability and functionality. Fabrication of materials that can interact with biomolecules like proteins necessitates the use of lipid bilayers as a mimic of cell membranes. ❧ The objective of this research is to develop novel hybrid lipid‐based nanostructures mimicking biological membranes. Toward this aim, two hybrid biocompatible structures are introduced: lipid bilayer‐coated multi‐walled carbon nanotubes (MWCNTs) and hydrogel‐anchored liposomes with double‐stranded DNA anchors. These structures have potential applications in biosensing, drug targeting, drug delivery, and biophysical studies of cell membranes. ❧ In the first developed nanostructure, lipid molecules are covalently attached to the surfaces of MWCNTs, and then, using a sonication process, a uniform lipid bilayer that supports the incorporation of membrane proteins is formed. These bilayer‐coated carbon nanotubes are highly dispersible and stable in aqueous solution, and they can be used in development of various biosensors and energy producing devices. ❧ In the other hybrid nanostructure, the lipid bilayer of a liposome is covalently anchored to a biocompatible poly(ethylene) glycol (PEG) hydrogel core using double‐stranded DNA (dsDNA) linkers. Release studies shows that nano‐size hydrogel‐anchored liposomes are exceptionally stable, and they can be used as biomimetic model membranes that mimic the connectivity between the cytoskeleton and the plasma membrane. After lipid bilayer removal, dsDNA linkers can provide programmable nanogels decorated with oligonucleotides with potential sites for further molecular assembly. These stable nanostructures can be useful for oligonucleotide and drug delivery applications. ❧ The developed hydrogel‐anchored liposomes are exploited for encapsulation and intracellular delivery of therapeutic peptide. Peptides with anti‐cancer properties are successfully encapsulated in hydrogel core of pH‐sensitive liposomes during rehydration process. Liposomes release their cargo at acidic pH. Confocal microscopy confirms the intracellular delivery of liposomes through an endocytotic pathway