Cell Adhesion in Cancer, Pathological Inflammation, and Drug Delivery
Cellular adhesion is the means by which cells bind to other cells or matrix proteins to form tissues and/or generate motion. At the molecular level, the adhesion is mediated by glycoproteins and/or glycolipids that protrude from the cell surface and form bonds with complementary constructs present on other cells or in the extracellular matrix. An aggregate of these non-covalent bonds supports a force that allows the cell to remain stationary or can be used by the cell as a means of locomotion. Cell adhesion is germane to a host of pathological processes, including cancer and pathological inflammation (e.g., arthritis). The research of three faculty members at Ohio University is directly related to cell adhesion.
According to the , one in four deaths in the United States is due to cancer. Identification of the molecular mediators of metastasis (the process by which cancer spreads through the body) is critical in the search for a cure, since five-year survival rates decline precipitously once a primary tumor has spread. The two main avenues of metastasis are through the vasculature and the lymphatics. Monica Burdick, assistant professor of chemical and biomolecular engineering, and her group are focused on developing a mechanistic understanding of the effects of fluid flow (blood and lymph) on cellular interactions pertinent to the distant and regional spread of cancer. Through the combined use of established and novel techniques in both glycobiology and biomedical engineering, they aim to identify molecular markers for cancer spread through the vascular and lymphatic system, characterize the functional role of those molecules (particularly in cell-to-cell adhesion), and define the kinetic and chemical requirements for binding to those molecules.
One of the main functions of leukocytes (white blood cells) is to fight infection and repair damaged tissue. Leukocytes continuously pass through the vasculature on the lookout for problems. Once a problem is found, the leukocytes accumulate at the site and destroy the invading organism and/or assist with wound repair. While this function is necessary for the organism’s survival, in pathological inflammation the leukocytes accumulate where they are not needed, which can lead to tissue damage and disease progression. David F. J. Tees, assistant professor of physics and astronomy, and his group are working to understand the biophysical mechanisms that govern leukocyte adhesion in the lungs during serious infection, when a significant number of leukocytes can get trapped in the lungs, leading to organ failure. Since a large number of the vessels of the lungs are smaller than the diameter of the leukocytes, the leukocyte undergoes significant deformation during transit through the lungs. The Tees lab uses micropipette aspiration to analyze the microrheology of leukocytes, which gives insight into their deformability. The biochemical adhesion that occurs between the leukocyte and the vessel wall may also play a role in the trapping. To gain insight into the biochemical adhesion, this group uses force probe microscopy to determine the force dependence of the bonds that mediate leukocyte adhesion. Finally, in collaboration with Douglas Goetz, professor of chemical and biomolecular engineering, the Tees group investigates the relationship between leukocyte deformation and biochemical adhesion.
