Aging and freezing of active nematic dynamics of cancer-associated fibroblasts by fibronectin matrix remodeling

Jacques, Cécile; Ackermann, Joseph; Bell, Samuel; Hallopeau, Clément; Gonzalez, Carlos Perez-; Balasubramaniam, Lakshmi; Trepat, Xavier; Ladoux, Benoît; Maitra, Ananyo; Voituriez, Raphael; Vignjevic, Danijela Matic

doi:10.1101/2023.11.22.568216

Cited by 4 publications

References 35 publications

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Novel imaging and biophysical approaches to study tissue hydraulics in mammalian folliculogenesis

Turley,

Leong,

Chan

2024

Biophys Rev

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A key developmental stage in mammalian folliculogenesis is the formation of a fluid-filled lumen (antrum) prior to ovulation. While it has long been speculated that the follicular fluid is essential for oocyte maturation and ovulation, little is known about the morphogenesis and the mechanisms driving the antrum formation and ovulation, potentially due to challenges in imaging tissue dynamics in large tissues. Misregulation of such processes leads to anovulation, a hallmark of infertility in ageing and diseases such as the polycystic ovary syndrome (PCOS). In this review, we discuss recent advances in deep tissue imaging techniques, machine learning and theoretical approaches that have been applied to study development and diseases. We propose that an integrative approach combining these techniques is essential for understanding the physics of hydraulics in follicle development and ovarian functions.

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Novel imaging and biophysical approaches to study tissue hydraulics in mammalian folliculogenesis

Turley,

Leong,

Chan

2024

Biophys Rev

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How cancer-associated fibroblasts promote T-cell exclusion in human lung tumors: a physical perspective

Ackermann,

Bernard,

Sirven

et al. 2024

Preprint

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The tumor stroma is a tissue composed primarily of extracellular matrix, fibroblasts, immune cells, and vasculature. Its structure and functions, such as nutrient support and waste removal, are altered during malignancy. Tumor cells transform the fibroblasts into cancer-associated fibroblasts, which have an important immunosuppressive activity, on which growth, invasion and metastasis depend. These activated fibroblasts appear to prevent immune cell infiltration into the tumor nest, thereby promoting cancer progression and inhibiting T cell-based immunotherapy. To better understand the biophysics of the tumor stroma and predict the evolution of cancer cells, we measure the density of different cell types in the stroma using immunohistochemistry stained tumor samples from lung cancer patients. We then incorporate these data, as well as known information on cell proliferation rates and relevant biochemical interactions, into a minimal biomechanical model. We quantify the complex dynamics between species as a function of the system properties, highlighting the inefficiency of immune cells and the fundamental role of activated fibroblasts. A spatio-temporal approach of the inhomogeneous environment and non-uniform cell distributions explains the fate of lung carcinomas. The model reproduces that, while cancer-associated fibroblasts act as a barrier to tumor growth, they also reduce the efficiency of the immune response. Our conclusion is that number of outcomes exist as a result of the competition between the characteristic times of cancer cell growth and the activity rates of the other species. For example, simulations reveal scenarios where tumor nests persist despite the presence of an efficient immune response.

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Mechanical stresses govern myoblast fusion and myotube growth

Le Toquin,

Dubey,

Ardaševa

et al. 2024

Preprint

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Myoblast fusion into myotubes is critical for muscle formation, growth and repair. While the cellular and molecular mechanisms regulating myoblast fusion are increasingly understood, the role of biomechanics in this process remains largely unexplored. Here, we reveal that a dynamic feedback loop between evolving cell mechanics and cell-generated stresses shape the fusion of primary myoblasts in vitro. Applying principles from active nematics, we show that myoblast and myotube patterning follows physical rules similar to liquid crystal organization. Remarkably, fusion predominantly occurs at comet-shaped topological defects in cellular alignment, which we identified as regions of high compressive stress. We further find that this stress-driven organization depends on extracellular matrix (ECM) deposition, which mirrors the nematic order of the cell population. Our integrated data, supported by active nematics-based mathematical modeling, accurately predict self-organization patterns and mechanical stresses that regulate myoblast fusion. By revealing the essential role of biomechanics and ECM interplay in myogenesis, this work establishes a foundational framework for understanding biomechanical principles in morphogenesis.

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Aging and freezing of active nematic dynamics of cancer-associated fibroblasts by fibronectin matrix remodeling

Cited by 4 publications

References 35 publications

Novel imaging and biophysical approaches to study tissue hydraulics in mammalian folliculogenesis

Novel imaging and biophysical approaches to study tissue hydraulics in mammalian folliculogenesis

How cancer-associated fibroblasts promote T-cell exclusion in human lung tumors: a physical perspective

Mechanical stresses govern myoblast fusion and myotube growth

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