Emergent collective organization of bone cells in complex curvature fields

Sebastien J.P. Callens*, Daniel Fan, Ingmar A.J. van Hengel, Michelle Minneboo, Pedro J. Díaz-Payno, Molly M. Stevens, Lidy E. Fratila-Apachitei, Amir A. Zadpoor

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

25 Citations (Scopus)
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Individual cells and multicellular systems respond to cell-scale curvatures in their environments, guiding migration, orientation, and tissue formation. However, it remains largely unclear how cells collectively explore and pattern complex landscapes with curvature gradients across the Euclidean and non-Euclidean spectra. Here, we show that mathematically designed substrates with controlled curvature variations induce multicellular spatiotemporal organization of preosteoblasts. We quantify curvature-induced patterning and find that cells generally prefer regions with at least one negative principal curvature. However, we also show that the developing tissue can eventually cover unfavorably curved territories, can bridge large portions of the substrates, and is often characterized by collectively aligned stress fibers. We demonstrate that this is partly regulated by cellular contractility and extracellular matrix development, underscoring the mechanical nature of curvature guidance. Our findings offer a geometric perspective on cell-environment interactions that could be harnessed in tissue engineering and regenerative medicine applications.

Original languageEnglish
Article number855
JournalNature Communications
Issue number1
Publication statusPublished - 3 Mar 2023

Bibliographical note

We are thankful to Milica Dostanic and Paul Motreuil-Ragot for initial discussions and assessment of the PDMS molding, to Prof. Urs Staufer from the Precision and Microsystems Engineering department at TU Delft for enabling the use of the Nanoscribe GT2 device, and to Dr. Fatma Ibis-Ozdemir for access to silane treatment. We are grateful to Dr. Jonathan Yeow, Dr. Jonathan Wojciechowski, and Dr. Florent Seichepine for helpful discussions regarding the PS substrate fabrication. We are grateful to the Facility for Imaging by Light Microscopy at Imperial College London for confocal microscopy. The research leading to these results has received funding from the European Research Council under an ERC starting grant (677575, A.A.Z.). S.J.P.C. also recognizes support through a Rubicon fellowship from the Dutch Research Council (019.211EN.025, S.J.P.C.). Further support is acknowledged from Medical Delta Program RegMed4D (P.J.D.P.) and from the Engineering and Physical Sciences Research Council (EP/T020792/1, S.J.P.C., M.M.S.).

Publisher Copyright:
© 2023, The Author(s).


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