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Updated: Jun 14, 2025
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All-optical Mechanobiology Interrogation of Yes-associated Protein in Human Cancer and Normal Cells using a Multi-functional System
Published on: December 20, 2021
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YAP phosphorylation within integrin adhesions: Insights from a computational model.
Hamidreza Jafarinia1, Lidan Shi2, Haguy Wolfenson2
1MERLN Institute for Technology-Inspired Regenerative Medicine, Department of Cell Biology-Inspired Tissue Engineering, Maastricht University, Maastricht, the Netherlands.
Biophysical Journal
|September 5, 2024
Summary
Yes-associated protein (YAP) phosphorylation, crucial for cell response, is influenced by adhesion size and dynamics. Our model shows smaller adhesions and higher diffusion increase phosphorylated YAP (pYAP), impacting apoptosis.
Area of Science:
- Cell Biology
- Biophysics
- Mechanobiology
Background:
- Yes-associated protein (YAP) mediates cellular responses to mechanical and biochemical cues.
- YAP plays a role in apoptosis, with phosphorylation at Y357 linked to nuclear translocation and cell death on soft substrates.
- YAP Y357 phosphorylation is reduced on stiff matrices within larger focal adhesions.
Purpose of the Study:
- To investigate the dynamics of YAP phosphorylation within integrin adhesions using a stochastic model.
- To explore how adhesion size, diffusion rates, and binding kinetics influence YAP phosphorylation.
- To elucidate the interplay of adhesion lifetime and dephosphorylation rates on pYAP levels.
Main Methods:
- Development of a stochastic model to simulate YAP phosphorylation dynamics.
- Analysis of the effects of cytosolic diffusion rate on phosphorylated YAP (pYAP) levels.
- Investigation of the impact of binding site availability and distribution on pYAP.
Main Results:
- Increased cytosolic diffusion rate of YAP correlates with elevated pYAP levels.
- Smaller adhesions (more binding sites) increase pYAP, especially at lower diffusion rates.
- Adhesion lifetime, binding/release rates, and dephosphorylation rates significantly modulate adhesion-size-dependent YAP phosphorylation.
Conclusions:
- Adhesion size and dynamics are critical factors in regulating YAP phosphorylation.
- The model provides insights into the mechanotransduction of YAP.
- Findings offer a basis for experimental validation of YAP phosphorylation regulation in cellular processes.
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