BME Graduate Seminar - Dr. Ian Schneider

Roy J. Carver Department of Biomedical Engineering Graduate Seminar (BME:5010)

Ian Schneider, PhD
Professor of Chemical and Biological Engineering
Iowa State University

Controlling Collagen Mechanical and Structural Properties in Tumor Microenvironment Mimics

Abstract: The tumor microenvironment (TME) is complex, consisting of many cell types that shape its structural and mechanical properties through the assembly of collagen fiber networks. Most normal tissue contains randomly oriented collagen fibers that form a relatively soft environment. As the tumor progresses, collagen is aligned perpendicularly to the tumor margin and is crosslinked to form a stiff extracellular matrix (ECM). Both structural and mechanical properties can modulate cell migration. Furthermore, aligned fibers and gradients in stiffness can direct cell migration towards particular targets in processes called contact guidance and durotaxis, respectively. Consequently, it is not surprising that high invasion and poor prognosis in both breast and pancreatic cancers correlate with aligned, stiff collagen. However, several questions remain. How do different cells in the TME respond to these directional cues? Do other components of the TME modulate these responses? Along with migration, cells can remodel the collagen fiber networks through degradation and force transmission, dramatically changing structure and mechanics. How do cells cooperate during this process and which molecular regulators alter the ECM from a tumor-promoting (stiff, aligned) to normal (soft, disorganized) ECM? In this talk I will present some approaches that we use to control structural and mechanical properties ex vivo in an attempt to mimic the TME. In addition, I will outline some insight into how cells migrate through or remodel the ECM in the TME. Understanding these cell responses will allow us to suggest approaches for either blocking invasion or reprogramming the ECM from tumor-promoting to tumor-inhibiting.