Confined cell migration along extracellular matrix space in vivo

• 成果类型: Article
• 署名作者: Chepizhko, Oleksandr; Armengol-Collado, Josep-Maria; Alexander, Stephanie; Wagena, Esther; Weigelin, Bettina; Giomi, Luca; Friedi, Peter; Zapperi, Stefano; La Porta, Caterina A. M.
• 署名单位: Leiden University; Leiden University - Excl LUMC; University of Texas System; UTMD Anderson Cancer Center; University of Wurzburg; University of Wurzburg; Radboud University Nijmegen; University of Milan; Consiglio Nazionale delle Ricerche (CNR); Istituto di Chimica della Materia Condensata e di Tecnologie per l Energia (ICMATE-CNR); University of Milan; IRCCS Ca Granda Ospedale Maggiore Policlinico; European Molecular Biology Laboratory (EMBL); European Molecular Biology Laboratory (EMBL); Eberhard Karls University of Tubingen
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-12019
• DOI: 10.1073/pnas.2414009121
• 发表日期: 2024-12-30
• 关键词: invasion; cancer; guidance

摘要

Collective migration of cancer cells is often interpreted using concepts derived from the physics of active matter, but the experimental evidence is mostly restricted to observations made in vitro. Here, we study collective invasion of metastatic cancer cells injected into the mouse deep dermis using intravital multiphoton microscopy combined with a skin window technique and three-dimensional quantitative image analysis. We observe a multicellular but low-cohesive migration mode characterized by rotational patterns which self-organize into antiparallel persistent tracks with orientational nematic order. We analyze the deformations induced by the cells in the extracellular matrix and find broadly distributed strain bands with a prevalence of compression. A model of active nematic hydrodynamics is able to describe several statistical features of the experimentally observed flow, suggesting that collective cancer cell invasion can be interpreted as a nematic active fluid in the turbulent regime. Our results help elucidate the migration patterns of cancer cells in vivo and provide quantitative guidance for the development of realistic in vitro and in silico models for collective cell migration.