11/17/2009
Department Seminar
11:45 AM
Whitaker 100
Gunjan Agarwal,
Ohio State University
"Multifaceted Regulation of Collagen by Discoidin Domain Receptors"
Collagen type 1 is the most abundant extracellular matrix protein present in the bone, connective tissue and vascular interstitium in adult tissues. The collagen fiber assembly is a complex multi-step process involving several intermediate stages. How the collagen morphology in these intermediate stages affects cell-matrix interactions and cellular physiology how different proteins and receptors interact with collagen to modulate collagen fibrillogenesis are questions not well understood. We present here how the collagen binding proteins, discoidin domain receptors (DDR1 and DDR2) interact with collagen and result in multi-faceted collagen regulation. DDRs are receptor tyrosine kinases expressed in a variety of mammalian cells including osteoblasts, fibroblasts, smooth muscle cells, endothelial cells and macrophages. We have recently established that the extracellular domain (ECD) of DDRs inhibits collagen fibrillogenesis. A significant delay in collagen fiber formation and disruption in the periodic banded structure of collagen fibers was observed in the presence of DDR ECDs using both purified proteins and cell-based assays. This disruption in collagen fiber morphology by DDRs leads to reduced mechanical strength of collagen fibers and also affects platelet-collagen interactions. We further demonstrate how interaction of collagen with DDRs is dependent on the fibrillar state of collagen and results in receptor oligomerization and endocytosis. Our studies encompass a wide variety of techniques including atomic force microscopy (AFM), transmission electron microscopy (TEM) and fluorescence resonance energy transfer (FRET) analysis for cell and molecular biology.
Biomedical Engineering
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