The Guthold lab is working on several projects in the general areas of Biophysics and nano- and bio-technology.
Major techniques we are using include atomic force microscopy (AFM) for imaging and manipulating molecules, laser scanning confocal fluorescence microscopy, and regular fluorescence microscopy (combined with the atomic force microscope), scanning electron microscopy (SEM), modern molecular biology techniques, such as gel electrophoresis (including Western blots), filtration techniques and protein and surface modification protocols, turbidimetry, electrospinning and cell culturing. Moreover, we collaborate with computational modeling groups.
In one project, we are investigating the mechanical and structural properties of fibrin fibers, which provide stability to blood clots. The overall goal is to increase understanding of hemostasis (healthy blood clotting) thrombotic disease (diseases caused by blood clots). Thrombotic disease, which underlies heart attacks, strokes, embolims and deep vein thrombosis, is the top cause of mortatily and disability worldwide. The image shows how a blood clot as it blocks blood flow in a heart attack (Image: NIH: National Heart, Lung and Blood Institute).
In a second project we are investigating the mechanical and morphological properties of cancer cells and normal cells, and understanding how a cell’s microenvironment affects these properties. The physical properties of cells complement genetic and biochemical information about the cells and provide a more complete picture about cell behavior. These physical traits may also point the way to new treatment options because of their possible role in the development and spread of cancer, i.e., metastasis. (Image: Confocal microscopy image of basall region of human mammary epithelial cells; image from Lee, H., K. Bonin, and M. Guthold, Human mammary epithelial cells in a mature, stratified epithelial layer flatten and stiffen compared to single and confluent cells. Biochimica et Biophysica Acta. General Subjects, 2021. 1865(6): p. 129891-129891).
In a third project, we are investigating the mechanical properties of electrospun fibers that may be used in tissue engineering and biomedical applications. (Image: Left, cylinder made from electrospun fibers (diameter ~ 1 cm); right, SEM image of electrospun fibers).
Additionally, Dr. Guthold is engaged in AFM imaging projects involving biological samples (e.g., DNA), nanostructures and organic electronics samples. The image shows an AFM scan of lambda DNA, M. Guthold).
In a fifth project, we are developing a novel, fast, high-throughput drug discovery technology. The technology utilizes a next-generation sequencing chip and nucleic acid-encoded chemicals.