The cells in cartilage and other soft tissues are surrounded by a soft matrix of molecules that the cells produce. The response of a cell to mechanical loading depends on the mechanical properties of this matrix. If it is soft or stiff will change whether the cell is protected from mechanical loadings or whether it is not. The mechanical loads on cells are known to modify the cell's production of matrix molecules and also to change how fast the cell produces repair molecules for cartilage. The matrix, therefore, helps to control how loads on cartilage (or other soft tissues) change the cell activity. This effect of the matrix will be analyzed in this Faculty Early Career Development Program (CAREER) research project. Education and outreach activities will be integrated with the research. A new course will be developed to increase the learning of biomechanics and nanotechnology for students at Drexel. The PI will give workshops on biomechanics for Philadelphia inner city high school teachers and students, and develop a science museum exhibition display with the structure-mechanics of connective tissues as the focus. The research will add knowledge of how mechanical loading effects cartilage metabolism, a key part of understanding and preventing cartilage diseases such as osteoarthritis.
This research will generate new knowledge on the biomechanics of the pericellular matrix (PCM) of fibrous tissues, to advance the understanding of fibrous tissue cell mechanotransduction. The fibrous tissue PCM is composed of porous collagen fibril network and proteoglycans (PGs). We hypothesize that this specialized PCM can attenuate cell strain under tension, and this function is mediated by its glycosaminoglycans (GAGs) on the PGs and the collagen fibril network. Using murine meniscus fibrous outer zone as the model tissue, we will test this hypothesis in two specific aims. In aim 1, we will test if removal of GAGs of the PCM reduces its compressive modulus, and thus, increases ECM-cell strain transmission and alters cell calcium signaling and metabolism under tension. In aim 2, we will alter the PCM collagen fibril structure by reducing the expression of collagen V in mice. We will test if loss of collagen V increases the PCM fibril alignment, and thus, cell strain transmission. These results will reveal the contribution of GAGs and collagen fibrils to the function of PCM in mediating cell mechanotransduction, achieving our overall goal.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
