Type: 
PhD Thesis Defense
Date-Time: 
Monday, November 25, 2019 - 11:00 to 13:00
Location: 
Yunker room
Event Speaker: 
Jihan Kim
Local Contact: 
Bo Sun
Abstract: 

Cell migration is fundamental for physiological processes such as immune re-sponses, wound healing and development. It is also a critical characteristic ofmetastatic cancer cells. An extensive amount of studies have focused on 2D sub-strates in order to understand the mechanism of cancer metastasis. However,much less is known about 3D cell migration due to the biophysical complexity of3D extracellular matrix (ECM). During 3D cell migration, cancer cells dynamicallyinteract with surrounding complex ECM. The relationship is bidirectional; cancercells remodel ECM and ECM modulates cancer cell migration. To quantify 3Dmicromechanical ECM remodeling induced by cell traction forces, we first developa traction microscopy method based on confocal reflection microscopy and partialvolume correlation (PVC) algorithm. Without introducing any labeled methods,our method allows us to stably quantify 3D ECM deformation fields around cancer cells. Next, we investigate further biophysical characteristics and mechanismof ECM remodeling due to cell contractility. The result shows that a pair of can-cer cells can remodel ECM between cells into significantly densified and alignedcollagen bundles. Collagen bundle formation is an irreversible process which iscontradictory to the commonly known elastic model. To explain the mechanismof irreversibility, we introduce a sliding and merging event of the ECM and de-velop a computational model. Next, we develop a circularly aligned 3D ECM tounderstand how remodeled ECM modulates cancer cell migration. It shows thatcoherence of local ECM fibers positively correlates with mesenchymal type migra-tory mode. At highly coherent ECM regions, cancer cells are twice as likely toswitch migratory mode from amoeboid to mesenchymal mode compared to lowcoherent ECM regions. Finally, we examine 3D migration of cancer organoidsin various geometrical shapes of ECM to understand collective cancer migration.The result shows that geometry of ECM regulates cancer invasion depth. We alsodevelop a computational model to explain how geometry influences cell migra-tion. Due to strong expansion and contraction induced by cancer organoids, ECMalignments are remodeled and the new alignments promote cancer migration. Ourstudy provides better understanding of bidirectional interactions between cells andECM by investigating the mechanism from single cell level to multicellular level.