New Nano-mechanical Approaches in Cancer Biology

Sara Ellias, Dr. Hoffmann, Dr. Fridman, Dr. Sundararaghavan, Department of Physics and Astronomy, Pathology, and Biomedical Engineering, Wayne State University, 42 W Warren Ave, Detroit, MI 48202

Understanding the responses of cancer cells to changes in their microenvironment is an important step towards personalizing treatment therapies. This requires an understanding of the relationship between cancer cell morphology, the surrounding environment, protein expression, and the effects that these factors have on the development of the disease. In this study, we are focusing on the relationship of cancer environment and the expression of an important receptor, Discoidin Domain Receptors (DDRs). DDR senses collagen, helping cancer cells to modify their environment. We will focus on Pancreatic Cancer (PC) cells, which overexpress DDR. PC cells promote the development of a collagen-dense scaffold and fibrosis - the hardening of tissue - which is associated with malignancy and drug resistance. The overall goal is to verify if disrupting DDRs in PC cells will impair the cancer cells’ ability to survive and proliferate. In particular, we seek to understand the relationship between DDR expression and cell behavior. Using a novel, recently-developed nano-mechanical technique, based on atomic force microscopy (AFM), the ligand binding and abundance of DDRs can be measured on live PC cells. PC cells, with and without DDR receptors, were seeded onto matrices made of collagen and hyaluronic acid. We developed hydrogel-based materials with varying mechanical and cell adhesion properties to mimic real tumor environments. Cell behavior on the materials were evaluated by measuring adhesion, cell morphology, proliferation, and cell phenotype. We investigated the relationship between DDR expression, cell behavior, type of environment, and receptor-ligand binding through an AFM technique that allows the measurement of cell receptor concentration and adhesion strength on each individual living cell. This project provides real-time insight into the molecular forces that govern DDR-collagen complexes in live cells, a key component in the development of rational therapeutic approaches that target DDR receptors. 

Additional Abstract Information

Presenter: Sara Ellias

Institution: Wayne State University

Type: Poster

Subject: Physics/Astronomy

Status: Approved

Time and Location

Session: Poster 9
Date/Time: Wed 12:00pm-1:00pm
Session Number: 6137