Cells migrate in our body from when we are first being formed to when we are recovering from injuries as well as when we are sick. For example, our primitive organs are formed by the movement of specific cells during the embryonic development. During immune response, immune cells move in search of foreign organisms to fight against infections. To close the open wounded site, epithelial cells migrate across the injured site while establishing new cell-cell contacts [1]. Although cell motility enables us to develop, cure and heal, it can also have negative implications as is the case in cancer metastasis. During cancer metastasis, cancer cells travel from their primary site to secondary sites, spreading the disease in our body. This metastatic behaviour of cancer accounts for 90% of cancer-related deaths. Previously, some studies have shown that cancer cells applied larger traction stresses than non-metastatic cells [2] while others have observed an inverse relationship between the metastatic potential and traction stresses [3]. Additionally, other studies have shown cancer cells are softer than benign cells [4]. These results suggest that there is a link between the cancer disease and cellular mechanics. In our studies, we would like to better understand the physical and mechanical changes in the cancer disease. 

One of the physical mechanisms we are particularly interested in is Epithelial to Mesenchymal Transition (EMT). An induction of EMT program has been proposed as a crucial mechanism for malignant epithelial cancer cells causing tumor cells to become more motile and invasive allowing them to spread in our body [5]. During the EMT process, epithelial cells lose their cell polarity and cell-cell adhesions while gaining mesenchymal properties including enhanced migratory and invasive behaviour. However, physical changes during EMT are still not well understood. We are interested in investigating how cell mechanics change during EMT process. Our research specifically focuses on how cellular forces and work change during EMT. In our studies, we examine how mechanical properties evolve during this transition utilizing soft silicone substrates. We are also interested in studying how cells change mechanical properties during EMT. To study the mechanical changes of the cells, we will utilize the magnetic twisting cytometry and the passive microrheology. Additionally, we investigate how cytoskeletal structures change as cells undergo EMT by focusing on the structural changes of actin stress fibers and it affects the changes in physical properties of the cells.

1.   Lodish, H., Molecular Cell Biology. W. H. Freeman: 2008.

2.   Kraning-Rush, C. M.; Califano, J. P.; Reinhart-King, C. A., Cellular traction stresses increase with increasing 

      metastatic potential. PloS one 2012, 7 (2).

3.   Indra, I.; Undyala, V.; Kandow, C.; Thirumurthi, U.; Dembo, M.; Beningo, K. A., An in vitro correlation of 

      mechanical forces and metastatic capacity. Physical biology 2011, 8 (1).

4.   Cross, S. E.; Jin, Y. S.; Rao, J.; Gimzewski, J. K., Nanomechanical analysis of cells from cancer patients. 

      Nature nanotechnology 2007, 2 (12), 780-3; (b) Guo, M.; Ehrlicher, A. J.; Jensen, M. H.; Renz, M.; Moore, J. R.; 

      Goldman, R. D.; Lippincott-Schwartz, J.; Mackintosh, F. C.; Weitz, D. A., Probing the stochastic, motor-driven 

      properties of the cytoplasm using force spectrum microscopy. Cell 2014, 158 (4), 822-32.

5.   Yilmaz, M.; Christofori, G., EMT, the cytoskeleton, and cancer cell invasion. Cancer Metastasis Rev Cancer 

      and Metastasis Reviews 2009, 28 (1-2), 15-33.

6.    Yoshie H, Koushki N, Molter C, Siegel PM, Krishnan R, Ehrlicher AJ. High Throughput Traction Force 

       Microscopy Using PDMS Reveals Dose-Dependent Effects of Transforming Growth Factor-β on the 

       Epithelial-to-Mesenchymal Transition. J Vis Exp. 2019 Jun 1;(148):10.3791/59364.