Coordination between Intra- and Extracellular Forces Regulates Focal Adhesion Dynamics.
Bibhu Ranjan SarangiMukund GuptaBryant L DossNicolas TissotFrance LamRené-Marc MègeNicolas BorghiBenoit LadouxPublished in: Nano letters (2016)
Focal adhesions (FAs) are important mediators of cell-substrate interactions. One of their key functions is the transmission of forces between the intracellular acto-myosin network and the substrate. However, the relationships between cell traction forces, FA architecture, and molecular forces within FAs are poorly understood. Here, by combining Förster resonance energy transfer (FRET)-based molecular force biosensors with micropillar-based traction force sensors and high-resolution fluorescence microscopy, we simultaneously map molecular tension across vinculin, a key protein in FAs, and traction forces at FAs. Our results reveal strong spatiotemporal correlations between vinculin tension and cell traction forces at FAs throughout a wide range of substrate stiffnesses. Furthermore, we find that molecular tension within individual FAs follows a biphasic distribution from the proximal (toward the cell nucleus) to distal end (toward the cell edge). Using super-resolution imaging, we show that such a distribution relates to that of FA proteins. On the basis of our experimental data, we propose a model in which FA dynamics results from tension changes along the FAs.
Keyphrases
- energy transfer
- single molecule
- single cell
- high resolution
- cell therapy
- stem cells
- quantum dots
- dna methylation
- escherichia coli
- mass spectrometry
- staphylococcus aureus
- binding protein
- machine learning
- pseudomonas aeruginosa
- living cells
- deep learning
- biofilm formation
- photodynamic therapy
- fluorescent probe
- cell adhesion