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In my second talk, I will describe research projects in my lab that deal with biomechanical signaling. Biomechanical signaling, as opposed to chemical signaling, is a new field investigating how cells transmit signals via mechanical means (forces), rather than chemical means. Biomechanical signaling can occur at the molecular, sub-cellular, cellular, intra-cellular and systems level, and it may be as important as chemical signaling.
1. Many current cancer therapeutics bind to DNA and induce structural changes by bending, unwinding, lengthening, softening, stiffening or crosslinking the DNA double helix. In essence many of these changes are mechanical in nature. Using statistical analysis of atomic force microscopy images and computer-simulated images, we can determine the mechanical changes, such as kinking, lengthening and stiffening/softening in a DNA double helix. These changes can be recognized by DNA binding proteins. We are currently investigating mechanical changes induced by the cancer therapeutic cis-platin and developing cancer therapeutic Pt-Acramtu.
2. Recent experiments have shown that mechanical signaling critically influences cell development and differentiation; for example undifferentiated cells grown on a soft matrix yield nerve cells, whereas cells on a hard matrix yield bone cells (Engler et al., 2006; Chowdhury et al., 2009). Cells are typically grown on a matrix of nanoscopic fibers, and, thus, the mechanical properties of these nanoscopic fibers may critically influence cell development and differentiation. We have developed an atomic force/optical microscopy-based technique to determine the mechanical properties of nanofibers, and used this technique to determine the properties of electrospun fibrinogen and collagen fibers. These fibers are used in tissue engineering scaffolds. In ongoing experiments we relate the mechanical properties of the nanofibers to cell growth on the matrix (scaffold).