Emergent mechanical control of vascular morphogenesis.

Autor: Whisler J; Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA., Shahreza S; Department of Mechanical Engineering, University College London, London, UK., Schlegelmilch K; Tumour Cell Biology Laboratory, Francis Crick Institute, London, UK., Ege N; Tumour Cell Biology Laboratory, Francis Crick Institute, London, UK.; Mnemo Therapeutics, 101 Boulevard Murat, 75016 Paris, France., Javanmardi Y; Department of Mechanical Engineering, University College London, London, UK., Malandrino A; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.; 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., Agrawal A; Department of Mechanical Engineering, University College London, London, UK., Fantin A; UCL Institute of Ophthalmology, University College London, London, UK.; Department of Biosciences, University of Milan, Via G. Celoria 26, 20133 Milan, Italy., Serwinski B; Department of Mechanical Engineering, University College London, London, UK.; 199 Biotechnologies Ltd., Gloucester Road, London W2 6LD, UK.; Northeastern University London, London, E1W 1LP, UK., Azizgolshani H; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA., Park C; Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA., Shone V; Experimental Histopathology Laboratory, Francis Crick Institute, London, UK., Demuren OO; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA., Del Rosario A; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA., Butty VL; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA., Holroyd N; UCL Centre for Advanced Biomedical Imaging, Paul O'Gorman Building, 72 Huntley Street, London, UK., Domart MC; Electron Microscopy Laboratory, Francis Crick Institute, London, UK., Hooper S; Tumour Cell Biology Laboratory, Francis Crick Institute, London, UK., Szita N; Department of Biochemical Engineering, University College London, London, UK., Boyer LA; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA., Walker-Samuel S; UCL Centre for Advanced Biomedical Imaging, Paul O'Gorman Building, 72 Huntley Street, London, UK., Djordjevic B; Department of Mechanical Engineering, University College London, London, UK.; 199 Biotechnologies Ltd., Gloucester Road, London W2 6LD, UK., Sheridan GK; School of Life Sciences, Queen's Medical Centre, University of Nottingham, Nottingham, UK., Collinson L; Electron Microscopy Laboratory, Francis Crick Institute, London, UK., Calvo F; Instituto de Biomedicina y Biotecnología de Cantabria (Consejo Superior de Investigaciones Científicas, Universidad de Cantabria), Santander, Spain., Ruhrberg C; UCL Institute of Ophthalmology, University College London, London, UK., Sahai E; Tumour Cell Biology Laboratory, Francis Crick Institute, London, UK., Kamm R; Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA., Moeendarbary E; Department of Mechanical Engineering, University College London, London, UK.; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.; 199 Biotechnologies Ltd., Gloucester Road, London W2 6LD, UK.
Jazyk: angličtina
Zdroj: Science advances [Sci Adv] 2023 Aug 11; Vol. 9 (32), pp. eadg9781. Date of Electronic Publication: 2023 Aug 11.
DOI: 10.1126/sciadv.adg9781
Abstrakt: 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.
Databáze: MEDLINE