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Alpha5beta1 integrin-fibronectin interactions specify liquid to solid phase transition of 3D cellular aggregates
Carlos E Caicedo-Carvajal1, Troy Shinbrot, Ramsey A Foty
1Department of Biomedical Engineering, Rutgers University, Piscataway, New Jersey, United States of America.
Plos One
|August 6, 2010
Summary
Interactions between fibronectin and integrin alpha5beta1 influence tissue cohesion, shifting mechanical properties from liquid to solid states. This dynamic interplay is crucial for embryonic development and wound healing.
Area of Science:
- Cell biology
- Biophysics
- Developmental biology
Background:
- Tissue organization relies on dynamic regulation of cell-cell and cell-extracellular matrix (ECM) adhesion.
- Integrins and cadherins mediate these adhesive interactions.
- Integrin alpha5beta1 and soluble fibronectin (sFN) are critical for cell-ECM force generation and ECM remodeling.
Purpose of the Study:
- To investigate the interplay between integrin alpha5beta1 and sFN.
- To determine how this interaction influences tissue mechanical properties and cell sorting behavior.
Main Methods:
- Generated cell lines with varying alpha5beta1 receptor densities.
- Utilized tissue surface tensiometry to assess aggregate biomechanical properties.
- Analyzed the effects of different sFN concentrations on tissue cohesion.
Main Results:
- Observed complex, biphasic tissue cohesion profiles resulting from integrin alpha5beta1 and sFN interactions.
- Demonstrated that increasing alpha5beta1 density from low to moderate levels enhances cohesion, transitioning tissue from viscoelastic-liquid to pseudo-viscoelastic-solid behavior.
- Found that excessive alpha5beta1 density leads to an abrupt decrease in cohesion, reverting to viscoelastic-liquid properties, potentially due to sFN depletion.
- Showed that differential alpha5beta1 integrin expression can induce cell phase separation.
Conclusions:
- The interplay between alpha5-integrin and sFN significantly impacts tissue cohesion and can modulate mechanical behavior (liquid to elastic).
- This interaction offers a tunable mechanism controlling tissue properties, influencing structure and function in biological processes.
- Findings provide insights applicable to embryonic development, wound healing, and tissue engineering.
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