Multi-tier mechanics control stromal adaptations in swelling lymph nodes

Assen FP, Hons M, Hauschild R, Shamipour S, Abe J, Kaufmann W, Costanzo T, Krens G, Brown M, Ludewig B, Hippenmeyer S, Stein JV, Heisenberg C-PJ, Hannezo EB, Luther SA, Sixt MK. Multi-tier mechanics control stromal adaptations in swelling lymph nodes. bioRxiv, 10.1101/2021.07.28.454217.


Preprint | Submitted | English
Abstract
Lymph nodes (LNs) comprise two main structural elements: Fibroblastic reticular cells (FRCs) that form dedicated niches for immune cell interaction and capsular fibroblasts that build a shell around the organ. While LNs are fairly stable in size during homeostatic conditions, immunological challenge causes more than 10-fold increase in size within only a few days. How a solid organ can accommodate such extreme volumetric changes is poorly understood. Here, we characterize the biomechanics of LN swelling on the cellular and organ scale. We identify lymphocyte trapping by influx and proliferation as drivers of an outward pressure force, causing FRCs and their associated conduits to stretch. After an initial phase of relaxation, FRCs sense the resulting strain via cell matrix adhesions, which coordinates local growth and remodeling of the stromal network. While the expanded FRC network adopts its typical configuration, a massive fibrotic reaction of the organ capsule sets in and counters further organ expansion. Thus, different fibroblast populations mechanically control LN swelling in a multi-tier fashion.
Publishing Year
Date Published
2021-07-31
Journal Title
bioRxiv
Acknowledgement
This research was supported by the Scientific Service Units of IST Austria through resources provided by the Bio Imaging, Electron Microscopy, Preclinical and Life Science Facilities. We thank Christine Moussion for providing anti-PNAd antibody, Simon Hippenmeyer and David Critchley for respectively donating transgenic MADM-7 and Talin1floxed mice, and Ekaterina Papusheva for providing a custom 3D channel alignment script. This work was supported by European Research Council grant ERC-CoG-72437.
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Cite this

Assen FP, Hons M, Hauschild R, et al. Multi-tier mechanics control stromal adaptations in swelling lymph nodes. bioRxiv. doi:10.1101/2021.07.28.454217
Assen, F. P., Hons, M., Hauschild, R., Shamipour, S., Abe, J., Kaufmann, W., … Sixt, M. K. (n.d.). Multi-tier mechanics control stromal adaptations in swelling lymph nodes. bioRxiv. Cold Spring Harbor Laboratory. https://doi.org/10.1101/2021.07.28.454217
Assen, Frank P, Miroslav Hons, Robert Hauschild, Shayan Shamipour, Jun Abe, Walter Kaufmann, Tommaso Costanzo, et al. “Multi-Tier Mechanics Control Stromal Adaptations in Swelling Lymph Nodes.” BioRxiv. Cold Spring Harbor Laboratory, n.d. https://doi.org/10.1101/2021.07.28.454217.
F. P. Assen et al., “Multi-tier mechanics control stromal adaptations in swelling lymph nodes,” bioRxiv. Cold Spring Harbor Laboratory.
Assen FP, Hons M, Hauschild R, Shamipour S, Abe J, Kaufmann W, Costanzo T, Krens G, Brown M, Ludewig B, Hippenmeyer S, Stein JV, Heisenberg C-PJ, Hannezo EB, Luther SA, Sixt MK. Multi-tier mechanics control stromal adaptations in swelling lymph nodes. bioRxiv, 10.1101/2021.07.28.454217.
Assen, Frank P., et al. “Multi-Tier Mechanics Control Stromal Adaptations in Swelling Lymph Nodes.” BioRxiv, Cold Spring Harbor Laboratory, doi:10.1101/2021.07.28.454217.
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