Actomyosin contractility confers mechanoprotection against tnfα-induced disruption of the intervertebral disc

Paula A. Hernandez, Timothy D. Jacobsen, Nadeen O. Chahine

Research output: Contribution to journalArticlepeer-review

Abstract

Inflammation triggers degradation of intervertebral disc extracellular matrix (ECM), a hallmark of disc degeneration that contributes to back pain. Mechanosensitive nucleus pulposus cells are responsible for ECM production, yet the impact of a proinflammatory microenvironment on cell mechanobiology is unknown. Using gain- and lossof- function approaches, we show that tumor necrosis factor-α (TNFα)-induced inflammation alters cell morphology and biophysical properties (circularity, contractility, cell stiffness, and hydraulic permeability) in a mechanism dependent on actomyosin contractility in a three-dimensional (3D) culture. We found that RhoA activation rescued cells from TNFα-induced mechanobiological disruption. Using a novel explant-in-hydrogel culture system, we demonstrate that nuclear factor kappa-B nuclear translocation and transcription are mechanosensitive, and its downstream effects on ECM degradation are regulated by actomyosin contractility. Results define a scaling relationship between circularity, contractility, and hydraulic permeability that is conserved from healthy to inflammatory microenvironments and is indicative of cell mechanobiological control across scales in 3D.

Original languageEnglish (US)
Article numbereaba2368
JournalScience Advances
Volume6
Issue number34
DOIs
StatePublished - Aug 2020

ASJC Scopus subject areas

  • General

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