Fabricating artificial cells and tissues
We are developing new approaches that use microfluidic and physical chemical techniques to assemble the molecules of cell membranes into structures that mimic the structure and behavior of cells. The image to the left shows a synthetic tissue formed by swelling a lipid film from the surface of a hydrogel. When the hydrogel contains detergent-solubilized intrisic membrane proteins, the cellular structures that form from the swollen lipid film incorporate this protein in their membranes.
These systems are useful for fundamental studies of membrane biophysics as well as drug discovery, diagnosis, and explorations of cell- and tissue-level systems biology.
We build microfluidic reactors that use droplet flows to generate high-quality precious metal nanoparticles. By customizing the surface chemistry of the microfluid channels, we are able to generate stable droplets at unusual high flow rates. The image at the right compares droplet formation at high flow rate in an uncoated channel (red outline) to that in a coated channel (blue outline) maximizing the droplet throughput allows us to build devices that can produce an industrially relevant yeild of nanoparticles.
Ongoing work on this project involves the development of new chemistry targets for microreactors and the creation of schemes for massive microfluidic parallelization. Massive parallelization has the potential to transform microreactors into a major industrial chemical technology.
Oxidative damage to cell membranes
Molecules in the cell membrane react readily with various reactive oxygen species, and damage to the membrane represent an important mechanism whereby oxidative stress results in biological harm. We use a broad set of tools and techniques to study how oxygen can damage cell membranes. This includes the direct observation of morphological transformations induced in giant unilamellar lipid vesicles (GUVs) during oxidation (see the series of images to the left) as well as chages in the permeability and phase structure of oxidized membranes.
By better understanding the physical chemistry of membrane oxidation, we hope to better understand diseases such as hyperbaric oxygen toxicity and a wide range of age-related disorders. Futher, we seek to discover new, membrane-based, therapies to counter oxidation damage.
Membrane permeability to small molecules
We study how cell membrane structure and composition affects the ability of small drug-like molecules to penetrate the membrane. The two times series on the right show the change in fluorescence inside a giant lipid vesicle as a weak organic acid (a) enters and (b) exists the vesicle. This work has implications for the rational design of drugs with high bioavailability.
Nanomaterial interactions with cell membranes
We study how nanoparticles interact with the cell membrane, leading to potential membrane damage. The image to the left shows protrusions forming on the surface of a model cell membrane as it is attacked by cationic polystyrene nanoparticles. The nanoparticles interact strongly with lipids in the membrane; this fluorescence micrograph shows the lipids labeled with a red dye and the nanoparticles labeled with a green dye. The protrusions formed include both lipids and nanoparticles.
As a result of the incorporation of lipid material in the protrusions, mechanical tension is applied to the cell membrane, leading to pore formation and membrane leakage.
Phase behavior of intrinsic membrane proteins
The lipid raft hypothesis holds that lipids in the cell membrane separate into distinct liquid phases, and that protein segregation to a specific phase controls protein function. We build model membranes consisting of phase-separating lipid mixtures and high concentrations of intrinsic membrane proteins to directly observe under what conditions proteins phase segregate. The image on the right shows the intrinsic membrane protein aquaporin SoPIP2;1 segregating to the liquid disorded phase in a model membrane.
Understanding the molecular interactions that lead to protein phase segregation in the membrane is a potential path to new therapies that directly target the lipid raft behavior of membrane proteins.
We develop methods and principles for constructing microfluidic circuits from modular fluidic and analytical components. These approaches allow for the rapid and straightforward design and assembly of fluidic systems for laboratory automation, miniature diagnostics, and high-throughput microreactors. 3D printing technology allows us to utilize standardized parts with three-dimensional complexity without having to rely on costly clean room fabrication methods.
The image to the left shows a 3D fluidic network assembled from modular blocks that snap together like LEGO bricks.