Thursday, 22 April 2021 | 3:00 pm
Professor & MEDx Investigator, Department of Biomedical Engineering, Mechanical Engineering and Materials Science Department of Orthopaedic Surgery, Pratt School of Engineering & Duke Medical Center, Durham, NC USA
Physicochemical properties of extracellular matrix: Key to function, Clue to mechanism
(Host: S. Zacchigna)
Reciprocal interactions of cells with their microenvironment are fundamental to multiple cellular processes necessary for tissue development, homeostasis, and regeneration. It is becoming increasingly apparent that while the extracellular environment normally maintains tissue homeostasis, but when negatively perturbed, it may also contribute to disease progression and age-dependent pathologies. In this talk, I will discuss our efforts to delineate the role of the ECM on various cellular responses relevant to tissue regeneration and disease progression. First, I will briefly talk about our efforts to create synthetic analogs of the ECM to direct stem cell commitment in vitro and in vivo and employ such engineered matrices as a platform to understand the molecular mechanism underlying stem cell differentiation (Shih et al., PNAS 111: 990, 2014; 114: 5419 2017; Kang H et al., Biomacromolecules 16: 1050, 2015). I will next talk about our recent efforts in understanding the role of extracellular matrix on cancer metastasis and fibrosis. Our findings show that the cells transition from a proteolytic-independent mode of invasion to a proteolytic-dependent mode upon an increase in the mechanical resistance from the extracellular environment (Aung A et al., Biophys. J 107:2528, 2014). By employing a cutaneous fibrosis model, we unraveled the role of elastic fibers and their components, which lie at the interface of tissue stiffness and inflammation, on fibrosis progression (Nakasaki M et al., Nature Communications 6: 8574, 2015). Surprisingly, interfering with the ECM organization to alter the elastin content and tissue stiffness to levels comparable to normal skin diminished the inflammatory response and abrogated the fibrotic phenotype. I will end by briefly introducing our efforts to develop healthy and disease tissue models in vitro as technological platforms to study basic concepts and screen and small molecules.