Biophysical force regulation in tumor cell invasion - by Mingming Wu
Mingming Wu Department of Biological and Environmental Engineering, Cornell University
Host: Cristina Marchetti | Contact: Matthias Merkel, email@example.com
In native states, animal cells of most types are surrounded by extracellular matrices (ECMs). Cells are physically linked to the ECM fibers via adhesion molecules. Indeed, mechanical interactions between animal cells and ECM critically regulate cell functions, and disruption of the cell-ECM crosstalk is implicated in pathologic processes including tumor progression and fibrosis. Physical forces that cells generate within a 3D ECM is a key mediator between the cell and its microenvironment. In this talk, I will describe efforts in my lab (biofluidics.bee.cornell.edu) in understanding how biophysical forces regulate cell-ECM interaction, and modulate cancer cell invasion within a three dimensional architecture. Two examples will be given. (1) Using a newly developed 3D traction force microscopy, we measure forces generated by single cells when embedded within natively derived collagen matrices. We find that fibrous nonlinear elasticity of collagen matrix enables a positive mechanical feedback between the cell and ECM, and promotes a long range cell-cell interaction. (2) Using a microfluidic model, we demonstrate that interstitial fluid flow stress regulates tumor cell invasion within an ECM. We find that cells change motility types when subjected to fluid flows. Our work begins to elucidate the basic governing principles of physical forces in mediating cell-ECM interactions at single cell level, and opens doors for modelling population level cell dynamics in 3D.