Functional Implications of An Altered Collagen Fiber Ultrastructure
Gunjan AgarwalCollagen type 1 is the most abundant extracellular matrix protein in adult tissues. The collagen fiber assembly is a complex multi-step process involving several intermediate stages. My research focus is to understand the collagen fiber structure and regulation at the molecular level and how it affects cell-matrix interactions and mechanical properties of the underlying tissue. In particular we are studying how discoidin domain receptors (DDR1 and DDR2) interact with collagen type 1. DDRs are receptor tyrosine kinases expressed in a variety of mammalian cells. We have elucidated that by binding to collagen DDRs inhibit the fibrillogenesis and native structure of collagen fibers. These are critical findings as the quantity and quality of collagen fibers can be altered in a number of pathologies. Our ongoing work aims to elucidate the functional consequences of an altered collagen fiber ultrastructure. In particular we aim to undersatnd how the collagen fiber ultrastructure impacts fiber mechanics, collagen mineralization and cell-matrix interactions.