Total internal reflection fluorescence microscope optics.
Research
We are broadly interested in cell biophysics and polymer engineering. Below you'll find a description of a variety of projects we're currently excited about with links to our relevant publications and posters providing more details.
Cell Biophysics
Cells sense and respond to the mechanical properties of the substrate they are grown on. Plastic dishes and glass slides are not a natural environment for cells. Using gels with tunable mechanical properties, we have shown that stem cells specify their lineage (towards neurons, muscle, or bone) based solely on the stiffness of the substrate they are grown on. In a related project, heart cells are shown to beat differently on surfaces with muscle-like stiffness than on those with the stiffness of scar tissue, as would be encountered following a heart attack.
Related publications
Cardio-myocyte Poster
Stem Cell Poster
Cysteine Shotgun
Reactive amino acids like cysteine can be labelled with fluorescent molecules so that they can be visualized in a fluorescence microscope or detected with optical spectroscopy. Cysteines that are buried in the core of a protein will not react as quickly as those on the surface and so looking at the fraction of cysteines that are labelled in different protein domains can be used to estimate those cysteines' exposure. By looking at changes in the amount of labelling, we identify mechanically sensitive proteins that undergo conformational changes when cells are sheared or are grown on stiff substrates. This new method allows us to observe forced protein unfolding inside of cells.
Related publications
Cys Shotgun Poster
Worm-like Micelles and Polymersomes
Diblock copolymers consist of two connected chains, one hydrophobic and one hydrophilic. When they are put in water they self-assemble to form structures that sequester the hydrophobic block away from the water with the hydrophilic part exposed. The precise structures that form depend on several parameters such as chain length, charge, salt concentration and pH in the solvent, and temperature. We have investigated this rich phase behavior as well as the mechanical properties of these fascinating nano-assemblies. More recently we have discovered a charge induced phase separation in binary mixtures of diblock copolymers that leads to spotted vesicles and striped worms.
Related publications
Polymersome Poster
Drug Delivery and Gene Therapy
The structures formed by diblock copolymers in water are not only fascinating, they are also useful. They are promising candidates for drug delivery applications in which a drug is either encapsulated in a polymeric carrier or attached directly to one of the diblock molecules. We are taking advantage of the shape control in these systems to see whether rods behave differently from spheres in terms of their lifetime in circulation and biodistribution to ultimately exploit these properties for treating disease or aiding gene therapy.
Related publications
Drug Delivery Poster
Immunocompatibility and "Markers of Self"
Macrophages are professional phagocytes that play an important role in innate and acquired immunity because they can recognize foreign particles and dying (apoptotic) cells. Phagocytosis occurs through the extension of the plasma membrane around an extracellular particle and subsequent internalization. The activation of immune cells such as macrophages is regulated through a balance between activating and inhibiting signals. A protein called CD47 is expressed in all tissues and has been implicated as a marker of "self." We are currently studying the cell biology of this process with the ultimate goal of using nature's marker of self in biomedical applications.
Related publications
Immunocompatibility Poster
Nanomechanics and Structure of Proteins and their Assemblies
In addition to the affects of mechanics on cells, we are also interested in more fundamental studies to understand how proteins and protein assemblies give rise to their exceptional mechanical properties. This will ultimately enable the engineering of better biomimetic materials for cell culture, tissue engineering, and other applications. We use atomic force microscopy (AFM) to study the mechanics of single protein molecules and, using a new hybrid fluorescence/AFM, study the structure of protein assemblies and the interactions of cells with their substrates at the micro- to nanoscale.
Related publications
Nanomechanics Poster
