Cells and tissues have evolved to thrive in an environment continually subjected to fluctuating physical constraints. For example, the constantly changing fluid dynamics of blood flowing past endothelial cells that line arteries and veins has caused these cells to develop a rapid-fire plasticity to external forces. The emerging discipline of molecular mechanochemistry addresses these adaptations, combining elements of biomechanics, molecular biology, and biophysics. In addition to gaining new insight into basic cell biology, the area is ripe with relevance to human health and biotechnology.
University of Pennsylvania Medical Center researchers are studying how cells sense, respond, and adapt to physical forces and how these responses are important to physiological and pathological mechanisms. "This line of investigation is helping us to discover key regulatory molecules important for preventive therapy in such diseases as atherosclerosis and hypertension," says Peter F. Davies, PhD, director of Penn’s newly formed Institute for Medicine and Engineering, an organizational blending of medical and engineering faculties to support research, education, and business initiatives for bioengineering projects. Davies will present a review of his laboratory’s latest findings at the 1998 American Association for the Advancement of Science annual meeting in Philadelphia in a session entitled, "How Mechanical Forces are Sensed, Generated, and Used by Cells."
"Cells are constantly monitoring their surrounding physical environment," remarks Davies. "Cardiac output, and hence blood flow, goes through natural variations throughout the day, as well as with exercise and stress. For example, if a certain tissue needs more blood, the artery to that tissue will dilate and allow more blood to flow through it." Dilation and constriction of vessels are ultimately controlled by shifts from one signal transduction pathway to another, involving gene expression and protein transcription in the affected endothelial cells. Davies’ lab is studying several endothelial-cell genes sensitive to blood flow and how the molecular pathways that govern them vary due to changing external forces.
Getting at the heart of blood-flow dynamics is also critical to understanding the localization of atherosclerotic lesions. "Eddies form at arterial branches–much like when a river branches–and that’s where arterial lesions develop, leading to heart attack and stroke," explains Davies. His research team has exposed endothelial cells in culture to fluid conditions much like vessel-branch vortices to better understand how cells respond to these circumstances. The aim of these investigations is to develop interventional drugs, gene-therapies, and better blood-clot-dissolving enzymes for diseased vessels.
Editor’s Note: Dr. Davies can be reached at 215-898-4647 or firstname.lastname@example.org The University of Pennsylvania Medical Center’s sponsored research and training ranks third in the United States based on grant support from the National Institutes of Health, the primary funder of biomedical research and training in the nation–$175 million in federal fiscal year 1997. In addition, for the third consecutive year, the institution posted the highest annual growth in these areas–17.6 percent–of the top ten U.S. academic medical centers. News releases from the University of Pennsylvania Medical Center are available to reporters by direct e-mail, fax, or U.S. mail, upon request. They are also posted electronically to the medical center website (http://www.m ed.upenn.edu), to EurekAlert! (http://www.eurekalert.org), sponsored by the American Association for the Advancement of Science.
University of Pennsylvania School of Medicine. February 1998.