I. Engineering Synthetic Biomembranes
What constitutes a biological cell and can we understand enough about its internal workings to produce an artificial life form? As the first step towards achieving this goal, we are working actively to develop novel methods to create synthetic lipid membranes and compartments. Our interest in this topic reflects our fascination with the process of self-assembly and directed assembly of compartments from colloidal particles and/or macromolecules. Such processes may have played a role in the origins of life.
i. PAPYRUS: Giant Lipid Vesicles, Polymersomes, and Fatty Acid Vesicles From Paper
Our group discovered a method for producing giant vesicles using commercially available filter and chromatography cellulose paper. Termed PAPYRUS, for Paper-Abbetted amPhiphile hYdRation in aqUeous Solutions, the method requires only lipids, paper, and an aqueous solvent. Despite the ubiquity of paper and its many reported uses for controlling fluid flow of reagents and chemicals in paper-based diagnostic devices, our group’s work is the first demonstration of the application of cellulose fibers in paper as a platform for the macromolecular self-assembly of lipids.
The PAPYRUS method is general and can produce liposomes in various aqueous media, including ionic media important for maintaining the activity of proteins and other fragile biological encapsulants. Furthermore, the sheer simplicity of the method, and the ease of manipulation of paper, makes massive parallelization and scale-up of the fabrication of giant liposomes practical. Our work in this topic ties in with our interest in how polysaccharides interact with lipid membranes.
We subsequently demonstrated that paper facilitates the growth of polymersomes and fatty acid vesicles and thus seems to abet the formation of vesicular structures from a wide variety lamellar-phase forming amphiphiles.
Other materials that we are exploring for fabricating synthetic membrane systems include oxidized poly(dimethyl)siloxane (ox-PDMS). Our recent publication provides a link between the two common surfaces used to prepare in vitro biomimetic phospholipid membranes — i) glass surfaces used predominantly in fundamental biophysical experiments, for which there is abundant physicochemical information, with ii) ox-PDMS, the dominant material used in practical, applications-oriented systems to build micro-devices, topographically-patterned surfaces, and biosensors where there is a dearth of information.
II. Phase transitions in biological materials
The role of extracellular polysaccharides/glycans for the proper functioning of cells is still largely mysterious. Using a multi-pronged approach with tools from surface science, analytical chemistry, and high resolution (temporal and spatial) optics, our group interrogates membrane dynamics and phase behavior close to criticality, as well as far from it. By understanding the interactions between extracellular polysaccharides and lipid membranes, we wish to design structures or materials that interact with membranes, be they in cells or in model systems, to engineer patterns that lead to prescribed functions.
III. Quantitative electronics-free biosensors
Mechanisms that quantify biological recognition events due to analyte-ligand binding are the core principle for many biosensing applications. Current techniques are fundamentally-limited to requiring modern electronics and electricity to convert molecular binding events into a quantitative signal. The lack of power-free quantitative biosensing is a significant gap in the field. In this project, we use physical modalities such as flow through porous media and magneto-Archimedes levitation and electroless deposition of metals to develop new biosensing plaforms that can provide quantitative readouts without requiring electronics.