Mechanochemical synchronization of force oscillations in connective tissue models
- 1Department of Physics, Friedrich-Alexander-Universitaet Erlangen-Nuernberg, Erlangen, Germany
Abstract
Cells in a tissue coordinate their behavior collectively by mechanical and chemical feedback with their surroundings. To study how such feedback mechanisms interact, we embed multicellular spheroids from mouse and primary human fibroblasts of different origin in 3D collagen matrices. Immediately after embedding, spheroids apply steadily increasing, radially symmetric, inward-directed forces to the surrounding matrix. Typically, within a few hours, collective force oscillations emerge with an average time interval of {approx}30 min. Similar force oscillations also arise in engineered, parallel-aligned microtissues attached to flexible pillars. Force oscillations propagate between neighboring cells as a mechanical wave, accompanied by calcium waves that travel at comparable speeds of several hundred m/min. Blocking gap junctions or mechanosensitive Piezo1 channels impairs these oscillations, indicating that calcium signaling contributes to their propagation. Their amplitude and frequency are regulated by integrin-mediated feedback in actin-rich protrusions and by ERK signaling, which also controls collective invasion into the surrounding matrix. Neighboring spheroids mechanically synchronize their force oscillations in phase and frequency over distances of up to {approx}2 mm without direct contact. Together, our results show that oscillatory mechanochemical feedback enables multicellular systems to coordinate force generation and invasive migration across cellular and millimeter length scales in 3D matrices.
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BibTeX
@misc{boehringer2026mechanochemical,
title = {{Mechanochemical synchronization of force oscillations in connective tissue models}},
author = {D. Boehringer and L. Vogler and C. Mark and P. L. Strissel and J. Roeder and D. Kah and L. Schween and O. Zajac and A. Haertl and L. Fischer and S. Budday and R. Gerum and H. Herrmann and L. Winter and G. Wiche and W. H. Goldmann and G. Cappello and D. M. Vignjevic and M. Balland and A. R. Boccaccini and R. Strick and I. Thievessen and T. Boudou and B. Fabry},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.18.759356},
url = {https://www.biorxiv.org/content/10.64898/2026.10.18.759356v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Mechanochemical synchronization of force oscillations in connective tissue models
AU - D. Boehringer
AU - L. Vogler
AU - C. Mark
AU - P. L. Strissel
AU - J. Roeder
AU - D. Kah
AU - L. Schween
AU - O. Zajac
AU - A. Haertl
AU - L. Fischer
AU - S. Budday
AU - R. Gerum
AU - H. Herrmann
AU - L. Winter
AU - G. Wiche
AU - W. H. Goldmann
AU - G. Cappello
AU - D. M. Vignjevic
AU - M. Balland
AU - A. R. Boccaccini
AU - R. Strick
AU - I. Thievessen
AU - T. Boudou
AU - B. Fabry
PY - 2026
DA - 2026/10/18
PB - bioRxiv
DO - 10.64898/2026.10.18.759356
UR - https://www.biorxiv.org/content/10.64898/2026.10.18.759356v1
AB - Cells in a tissue coordinate their behavior collectively by mechanical and chemical feedback with their surroundings. To study how such feedback mechanisms interact, we embed multicellular spheroids from mouse and primary human fibroblasts of different origin in 3D collagen matrices. Immediately after embedding, spheroids apply steadily increasing, radially symmetric, inward-directed forces to the surrounding matrix. Typically, within a few hours, collective force oscillations emerge with an average time interval of {approx}30 min. Similar force oscillations also arise in engineered, parallel-aligned microtissues attached to flexible pillars. Force oscillations propagate between neighboring cells as a mechanical wave, accompanied by calcium waves that travel at comparable speeds of several hundred m/min. Blocking gap junctions or mechanosensitive Piezo1 channels impairs these oscillations, indicating that calcium signaling contributes to their propagation. Their amplitude and frequency are regulated by integrin-mediated feedback in actin-rich protrusions and by ERK signaling, which also controls collective invasion into the surrounding matrix. Neighboring spheroids mechanically synchronize their force oscillations in phase and frequency over distances of up to {approx}2 mm without direct contact. Together, our results show that oscillatory mechanochemical feedback enables multicellular systems to coordinate force generation and invasive migration across cellular and millimeter length scales in 3D matrices.
ER -