Emergent mechanical control of vascular morphogenesis-Reference-Cited by-同舟云学术

Emergent mechanical control of vascular morphogenesis

Published:2023-08-11 Issue:32 Volume:9 Page:
ISSN:2375-2548
Container-title:Science Advances
language:en
Short-container-title:Sci. Adv.

Author:

Whisler Jordan¹^ORCID,Shahreza Somayeh²^ORCID,Schlegelmilch Karin³^ORCID,Ege Nil³⁴^ORCID,Javanmardi Yousef²^ORCID,Malandrino Andrea⁵⁶,Agrawal Ayushi²^ORCID,Fantin Alessandro⁷⁸^ORCID,Serwinski Bianca²⁹¹⁰,Azizgolshani Hesham⁵,Park Clara¹^ORCID,Shone Victoria¹¹^ORCID,Demuren Olukunle O.¹²,Del Rosario Amanda¹³^ORCID,Butty Vincent L.¹²^ORCID,Holroyd Natalie¹⁴^ORCID,Domart Marie-Charlotte¹⁵^ORCID,Hooper Steven³,Szita Nicolas¹⁶,Boyer Laurie A.⁵¹²^ORCID,Walker-Samuel Simon¹⁴^ORCID,Djordjevic Boris²⁹,Sheridan Graham K.¹⁷^ORCID,Collinson Lucy¹⁵^ORCID,Calvo Fernando¹⁸,Ruhrberg Christiana⁷^ORCID,Sahai Erik³^ORCID,Kamm Roger¹⁵^ORCID,Moeendarbary Emad²⁵⁹^ORCID

Affiliation:

1. Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.

2. Department of Mechanical Engineering, University College London, London, UK.

3. Tumour Cell Biology Laboratory, Francis Crick Institute, London, UK.

4. Mnemo Therapeutics, 101 Boulevard Murat, 75016 Paris, France.

5. Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.

6. Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Engineering and Research Center for Biomedical Engineering, Universitat Politècnica de Catalunya (UPC), Av. Eduard Maristany, 10-14 08019 Barcelona, Spain.

7. UCL Institute of Ophthalmology, University College London, London, UK.

8. Department of Biosciences, University of Milan, Via G. Celoria 26, 20133 Milan, Italy.

9. 199 Biotechnologies Ltd., Gloucester Road, London W2 6LD, UK.

10. Northeastern University London, London, E1W 1LP, UK.

11. Experimental Histopathology Laboratory, Francis Crick Institute, London, UK.

12. Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA.

13. David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.

14. UCL Centre for Advanced Biomedical Imaging, Paul O'Gorman Building, 72 Huntley Street, London, UK.

15. Electron Microscopy Laboratory, Francis Crick Institute, London, UK.

16. Department of Biochemical Engineering, University College London, London, UK.

17. School of Life Sciences, Queen’s Medical Centre, University of Nottingham, Nottingham, UK.

18. Instituto de Biomedicina y Biotecnología de Cantabria (Consejo Superior de Investigaciones Científicas, Universidad de Cantabria), Santander, Spain.

Abstract

Vascularization is driven by morphogen signals and mechanical cues that coordinately regulate cellular force generation, migration, and shape change to sculpt the developing vascular network. However, it remains unclear whether developing vasculature actively regulates its own mechanical properties to achieve effective vascularization. We engineered tissue constructs containing endothelial cells and fibroblasts to investigate the mechanics of vascularization. Tissue stiffness increases during vascular morphogenesis resulting from emergent interactions between endothelial cells, fibroblasts, and ECM and correlates with enhanced vascular function. Contractile cellular forces are key to emergent tissue stiffening and synergize with ECM mechanical properties to modulate the mechanics of vascularization. Emergent tissue stiffening and vascular function rely on mechanotransduction signaling within fibroblasts, mediated by YAP1. Mouse embryos lacking YAP1 in fibroblasts exhibit both reduced tissue stiffness and develop lethal vascular defects. Translating our findings through biology-inspired vascular tissue engineering approaches will have substantial implications in regenerative medicine.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Link

https://www.science.org/doi/pdf/10.1126/sciadv.adg9781

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