Beyond 2D: Collective Cell Migration and Topological Data Analysis

ABSTRACT:

Epithelial cell migration is shaped by extracellular matrix architecture during development and disease, but the extracellular matrix is also dynamically remodeled by epithelial cells. Here, I present recent results from my group on the so-called epithelial-mesenchymal transition, whereby cells weaken cell-cell adhesions and gain a pro-invasive phenotype. First, we analyze the disorganization and dissemination of multicellular clusters cultured in 3D matrix, which exhibit both collective and individual invasion phenotypes with spatially non-uniform traction signatures. Second, we elucidate how larger multicellular spheroids transition from coordinated circumferential orbiting towards radial matrix invasion. Finally, we describe the use of topological barcodes for machine learning of tissue architecture based on spatial connectivity (i.e. persistent homology). We envision new insights into the dynamic reciprocity that emerges between cells and their physical microenvironment via mechanobiology and AI / ML approaches.

BIO:

Ian Wong is Associate Professor of Engineering, and of Pathology / Laboratory Medicine at Brown University. He engineers new miniaturized technologies based on biomaterials and microfluidics to investigate cancer cell invasion, drug resistance, and heterogeneity. He is also interested in the unconventional fabrication of bio and nano materials using self-assembly and 3D printing. He did his graduate work on the directed self-assembly of biomolecular materials with Nick Melosh, receiving a Ph.D. in Materials Science and Engineering from Stanford University. His postdoctoral training was with Mehmet Toner and Daniel Irimia at the Center for Engineering in Medicine at Massachusetts General Hospital. He has been recognized with an NSF Graduate Research Fellowship, a Damon Runyon Cancer Research Fellowship, the Brown University Pierrepont Award for Outstanding Advising and the Fain Engineering Faculty Research Award.