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Published on: June 2, 2017
Vinculin facilitates cell invasion into three-dimensional collagen matrices.
Claudia T Mierke1, Philip Kollmannsberger, Daniel Paranhos Zitterbart
1Center for Medical Physics and Technology, Biophysics Group, Friedrich-Alexander-University of Erlangen-Nuremberg, 91052 Erlangen, Germany. claudia.mierke@t-online.de
Vinculin enhances cell invasion in 3D matrices by increasing adhesion and traction forces. Vinculin knockout cells show increased 2D motility but reduced 3D invasion, highlighting vinculin's role in overcoming extracellular matrix (ECM) barriers.
Area of Science:
- Cell Biology
- Biophysics
- Extracellular Matrix Dynamics
Background:
- Vinculin (protein) links the actomyosin cytoskeleton to the extracellular matrix (ECM) via integrins.
- Vinculin influences cell adhesion dynamics and reduces cell motility on 2D ECM substrates.
- The role of vinculin in three-dimensional (3D) ECM invasion remains unclear.
Purpose of the Study:
- To investigate the effect of vinculin expression on cell invasion through dense 3D collagen matrices.
- To compare the motility and invasiveness of vinculin knockout and wild-type cells in 2D and 3D ECM environments.
Main Methods:
- Utilized vinculin knockout and wild-type mouse embryonic fibroblasts.
- Assessed cell motility on 2D collagen-coated substrates.
- Quantified cell invasion into 3D collagen matrices of varying densities (2.4 mg/ml and 5.8 mg/ml).
- Measured cell mechanical properties and cytoskeletal remodeling.
Main Results:
- Vinculin knockout cells exhibited 2-fold higher motility on 2D substrates but were 3-fold less invasive in 3D collagen matrices.
- Vinculin knockout cells were softer and showed more dynamic cytoskeletal remodeling.
- Vinculin-expressing cells displayed stronger adhesion to collagen and generated 3-fold higher traction forces.
- Vinculin-expressing cells successfully invaded dense 3D matrices (5.8 mg/ml) impenetrable to vinculin knockout cells.
Conclusions:
- Vinculin facilitates 3D matrix invasion by increasing traction forces necessary to overcome ECM steric hindrance.
- Vinculin expression is crucial for efficient cell migration and invasion in complex 3D environments.
- The differential effects of vinculin on 2D vs. 3D cell migration underscore its context-dependent roles in cell mechanics and motility.
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