This award to Wayne State University is for the acquisition of an integrated fluorescence and atomic force microscope to create a new platform to perform nanoscale measurements of cell-particle interactions. AFM is a force-measuring and surface imaging technique that can provide very high spatial resolution, while fluorescence microscopy provides fast, large scale and specific imaging of cells. By combining the two, (1) single molecule force measurements will be correlated with biological microenvironments or events, (2) simultaneous fluorescence and AFM imaging for a fuller picture of biological systems and their dynamics will be perform, and (3) sophisticated fluorescence techniques, such as Förster resonance energy transfer (FRET), can be correlated with AFM to measure applied forces to changes in structure. The combined instrumental platform will be used for interdisciplinary projects including single molecule interactions on live cells, optimization of DNA release from engineered polymer systems, cell motility studies, interactions of pathogens with cell surfaces, detection of food-borne bacteria, and dynamics and transport of magnetic nanoparticles in live cells.
The new instrumental platform will be a user facility, available to researchers in physics, materials science, biomedical engineering, biology, chemistry, the basic medical sciences, and beyond. The collaborative use of this instrument is expected to foster interactions between different disciplines, and thus create new opportunities and ideas. The proposed research has clear potential to lead to new technologies and benefit human health. The new platform will be integrated into an advanced biophysics lab course, part of the Wayne State University undergraduate Biomedical Physics Program, which impacts a significant number of people from underrepresented groups. As a user facility, this new instrument will help to train and inspire future scientists and engineers.
The goal of this project has been to create a new research facility for interdisciplinary research in biomaterials, bio-engineering and the biosciences. The facility is unique as it combines several powerful instruments into one package, allowing for probing biological and materials samples at the micro- and nanometer scale using several measurement techniques simultaneously. The new facility combines fluorescence microscopy and atomic force microscopy (AFM) into one instrument. Fluorescence microscopy has many application in biology, including locating specific biomolecules, and observing molecular motion and chemical reactions. AFM is used to provide very high resolution imaging and is capable of measuring small forces down to the minute forces acting between single molecules. The combined capabilities of these powerful techniques are made available to researchers from many different fields, including the basic sciences (physics, chemistry and biology), engineering and medicine. Initial projects currently underway with the new instrument include measurements of the interactions of cell receptors in cancer cells, structural properties of nanoparticles for RNA delivery for therapeutic purposes, and measurements of the structure and mechanical properties of fibers for neural tissue engineering. This new combined instrument enables researchers to perform experiments that are not possible when the two instruments are only available separately. For example, using simultaneous force and fluorescence measurements, scientists can measure the effect of mechanical deformations on cell structure or target specific cell membrane regions for measurements of single-molecule interactions between surface receptors on a cell and a drug that interacts with the receptor. The instrument serves as a training ground for future scientists and engineers. Students at the undergraduate and graduate level are being trained on the new instrument. Training our students on this instrumentation enhances their competitiveness and prepares them for cutting-edge research positions. The instrument also enables the development and evaluation of new technologies in the areas of biomaterials, nano-medicine, cancer therapeutics and drug delivery.
