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Tunable Hybrid Matrices Drive Epithelial Morphogenesis and YAP Translocation
Ying Zhang1,2, Mirjam M P Zegers3, Anika Nagelkerke2,4
1Institute for Molecules and Materials Radboud University Heyendaalseweg 135 Nijmegen 6525 AJ The Netherlands.
Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|January 29, 2021
Summary
Researchers developed hybrid hydrogels to control cell shape and function during development. These materials precisely tune stiffness and cell-matrix interactions, guiding Madin-Darby Canine Kidney (MDCK) cell morphogenesis.
Area of Science:
- Biomedical Engineering
- Developmental Biology
- Materials Science
Background:
- Morphogenesis is crucial for tissue function and involves cells responding to environmental cues.
- Epithelial cells display distinct 2D and 3D morphologies influenced by biochemical and biophysical signals.
- Understanding how physical factors regulate cell shape is key to developmental biology.
Purpose of the Study:
- To create a tailorable hybrid hydrogel system for studying cell morphogenesis.
- To investigate the impact of matrix stiffness and cell-matrix interactions on Madin-Darby Canine Kidney (MDCK) cell morphology.
- To explore the role of Yes-associated protein (YAP) translocation in response to matrix properties.
Main Methods:
- Fabrication of hybrid hydrogels combining Matrigel with synthetic oligo(ethylene glycol)-grafted polyisocyanides (PICs).
- Systematic variation of hydrogel stiffness and cell-adhesive peptide density.
- Culturing Madin-Darby Canine Kidney (MDCK) cells in 2D and 3D hybrid matrices.
- Analysis of cell morphology and Yes-associated protein (YAP) localization.
Main Results:
- Low matrix stiffness induced a shift from hollow cysts to 2D monolayers without YAP translocation.
- Higher stiffness and increased cell-matrix interactions promoted flattened cell morphology and YAP translocation.
- 3D cultures in these matrices resulted in the formation of tubular structures.
- Hybrid hydrogels offer precise control over cell morphology and YAP activation.
Conclusions:
- Hybrid hydrogels provide a versatile platform for dissecting the physical regulation of morphogenesis.
- External physical factors, such as stiffness and adhesion, can precisely control cell shape and tissue development.
- This system advances the study of Madin-Darby Canine Kidney (MDCK) cell morphogenesis and holds potential for complex tissue engineering.
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