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Prof Ming Guo

MIT

Biomechanical imaging of cells, extracellular matrix, and cancer invasion in 3D

Sculpting of structure and function of three-dimensional multicellular tissues depend critically on the spatial and temporal coordination of cellular physical properties. Yet the organizational principles that govern these events, and their disruption in disease, remain poorly understood. Here, I will introduce several of our recent work in understanding cell and extracellular matrix (ECM) mechanics, as well as their mechanical interactions in 3D. I will then focus on discussing a recent progress to map the spatial and temporal evolution of positions, motions, and physical characteristics of individual cells throughout a growing mammary cancer model. Compared with cells in the tumor core, cells at the tumor periphery and the invasive front are found to be systematically softer, larger and more dynamic. These mechanical changes are shown to arise from supracellular fluid flow through gap junctions, suppression of which delays transition to an invasive phenotype. Together, these findings highlight the role of spatiotemporal coordination of cellular physical properties in tissue organization and disease progression. In addition, I will introduce our recent progress on experimentally characterizing the local matrix stiffening induced by contraction of individual living cells inside a 3D biopolymer matrix, and will also introduce a method, called Nonlinear Stress Inference Microscopy, with which we can determine the cell-induced local matrix stress from nonlinear microrheology measurements inside various types of extracellular matrix in 3D.