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Matrix mechanical plasticity regulates cancer cell migration through confining microenvironments

Author

Listed:
  • Katrina M. Wisdom

    (Stanford University)

  • Kolade Adebowale

    (Stanford University)

  • Julie Chang

    (Stanford University)

  • Joanna Y. Lee

    (Stanford University)

  • Sungmin Nam

    (Stanford University)

  • Rajiv Desai

    (Harvard University)

  • Ninna Struck Rossen

    (Stanford University)

  • Marjan Rafat

    (Stanford University)

  • Robert B. West

    (Stanford University)

  • Louis Hodgson

    (Gruss-Lipper Biophotonics Center, Albert Einstein College of Medicine)

  • Ovijit Chaudhuri

    (Stanford University)

Abstract

Studies of cancer cell migration have found two modes: one that is protease-independent, requiring micron-sized pores or channels for cells to squeeze through, and one that is protease-dependent, relevant for confining nanoporous matrices such as basement membranes (BMs). However, many extracellular matrices exhibit viscoelasticity and mechanical plasticity, irreversibly deforming in response to force, so that pore size may be malleable. Here we report the impact of matrix plasticity on migration. We develop nanoporous and BM ligand-presenting interpenetrating network (IPN) hydrogels in which plasticity could be modulated independent of stiffness. Strikingly, cells in high plasticity IPNs carry out protease-independent migration through the IPNs. Mechanistically, cells in high plasticity IPNs extend invadopodia protrusions to mechanically and plastically open up micron-sized channels and then migrate through them. These findings uncover a new mode of protease-independent migration, in which cells can migrate through confining matrix if it exhibits sufficient mechanical plasticity.

Suggested Citation

  • Katrina M. Wisdom & Kolade Adebowale & Julie Chang & Joanna Y. Lee & Sungmin Nam & Rajiv Desai & Ninna Struck Rossen & Marjan Rafat & Robert B. West & Louis Hodgson & Ovijit Chaudhuri, 2018. "Matrix mechanical plasticity regulates cancer cell migration through confining microenvironments," Nature Communications, Nature, vol. 9(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-06641-z
    DOI: 10.1038/s41467-018-06641-z
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    Cited by:

    1. Woojin Choi & Utkarsh Mangal & Jae-Hun Yu & Jeong-Hyun Ryu & Ji‑Yeong Kim & Taesuk Jun & Yoojin Lee & Heesu Cho & Moonhyun Choi & Milae Lee & Du Yeol Ryu & Sang-Young Lee & Se Yong Jung & Jae-Kook Cha, 2024. "Viscoelastic and antimicrobial dental care bioplastic with recyclable life cycle," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    2. Julian C. Bahr & Xiao-Yan Li & Tamar Y. Feinberg & Long Jiang & Stephen J. Weiss, 2022. "Divergent regulation of basement membrane trafficking by human macrophages and cancer cells," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
    3. Karen L. Xu & Nikolas Caprio & Hooman Fallahi & Mohammad Dehghany & Matthew D. Davidson & Lorielle Laforest & Brian C. H. Cheung & Yuqi Zhang & Mingming Wu & Vivek Shenoy & Lin Han & Robert L. Mauck &, 2024. "Microinterfaces in biopolymer-based bicontinuous hydrogels guide rapid 3D cell migration," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

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