Global versus local matrix remodeling drives rotational versus invasive collective migration of epithelial cells
Year: 2024
Type: article
Abstract: The coordinated movement of cell collectives is essential for normal epithelial tissue development and maintenance, as well as the progression of many cancers. Our current understanding emphasizes that the initiation of collective migration behaviors requires adherens junctions. Moreover, the formation of cylindrical ductal tissues by invasive collective migration (ICM) or spherical acinar tissues by rotational collective migration (RCM) is directed by local changes in the adherens-mediated tension of the cell collective. Here, we report on a minimal 3D extracellular matrix (ECM) system wherein both ICM and RCM arise spontaneously from individually seeded epithelial cells, regardless of whether the cells express adherens junctions. Using a Cellular Potts model, we show that in confining 3D ECM, the localization of matrix remodeling activity can drive differences in cell polarization and protrusion dynamics that distinguish RCM and ICM. Quantitative microscopy experiments show that distinct matrix remodeling localization patterns are indeed coupled to initial differences in cell protrusion length, lifetime, and rate that dictate cell shape, which propagates across cell division cycles and gives rise to RCM and ICM behavior. These experiments reveal that matrix remodeling activity by MMPs is localized to the base of protrusions in cells initiating ICM, whereas RCM is associated with remodeling activity that is localized globally around the cell body. Broad-based inhibition of matrix metalloproteinases (MMPs) enriches for RCM and global matrix remodeling. Loss of ITGβ1 abrogates global matrix remodeling and RCM. These findings indicate that in confining 3D environments, distinct matrix remodeling strategies can encode collective cell migration behaviors and tissue structure outcomes independently of adherens junctions.
Source: Developmental Cell
Authors: Sural K. Ranamukhaarachchi, Alyssa Walker, Man-Ho Tang, William D. Leineweber, Sophia Lam, Wouter-Jan Rappel, Stephanie I. Fraley
Institution: University of California San Diego
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $9,350
Awards: CAREER: A multi-scale, data-driven model of 3D cell motility, Regulation of Collective Breast Cancer Invasion and Metastasis, Integrating Four-Dimensional Cell Migration Modeling with Quantitative Experiments, University of California San Diego Neuroscience Microscopy Imaging Core, G639426234, G6671297155, UCSD Cancer Center Training Program in Drug Development, The Cancer Cell Map Initiative v2.0
OpenAlex ID: W4405567869