Trends in Cell Biology
ReviewThe inner lives of focal adhesions
Section snippets
The second dimension of focal adhesions
In focal adhesions, the actin cytoskeleton is linked through various adaptor proteins to heterodimeric receptors of the integrin family (Fig. 1a) [19]. Integrin receptors bind to extracellular matrix proteins organized in either basement membranes (Fig. 1a) or connective tissues (Fig. 1b). Importantly, whether a focal adhesion is formed on a flat surface (e.g. glass coverslip) or within a network of extracellular-matrix proteins, the integrin receptors are confined to the 2D plane of the plasma
Using a 2D GFP–β3-integrin marker
The two examples of changing intensities of the focal adhesion markers GFP–vinculin and GFP–zyxin show dramatically that focal adhesions are complex structures that require multiple functional parameters to describe their behaviour, such as fluorescence intensity, traction forces and focal adhesion mobility (also termed ‘sliding’ [13]). When a 2D GFP–β3-integrin marker is used to study focal adhesions, the respective fluorescence intensity correlates directly with the packing ‘density’ of this
Elasticity and spacing of extracellular-matrix ligands
Anybody who has cultured cells on a plastic dish will have realized that, although cells spread, adhere and divide, they will, in living tissues, encounter non-homogeneous microenvironments consisting of rigid as well as flexible domains. Therefore, experiments in which cells have been cultured on elastic substrates have provided interesting information about the cellular responses within a flexible environment. Fibroblasts plated on a flexible substrate were unable to adhere tightly and
FRAP analysis reveals the dynamic interior of focal adhesions
The model of focal adhesion behaviour and mechanical signaling presented here is based on the notion that the initial stress-induced physical distortion of focal adhesions causes changes in their densities and subsequent recruitment of signaling and structural focal adhesion proteins. Although this model explains many of the experimental findings, it does not explain the observed mobility (‘sliding’) of focal adhesions 11., 13.. One of the best techniques for measuring the internal dynamics of
Concluding remarks
We have proposed here that new models to explain focal adhesion structure, function and regulation require the analysis of functional criteria such as focal adhesion density, renewal and the amount of traction force. Nevertheless, much work remains to be done to identify the regulatory pathways involved in focal adhesion dynamics and mechanical signaling. Although it is plausible that the physical distortion of focal adhesions is at the root of mechanical signaling, it is not known which
Acknowledgements
We thank Caroline Johnson-Léger, Caroline Cluzel, Michel Aurrand-Lions and Boris Hinz for stimulating discussions. Special thanks to Christoph Ballestrem for his tenacity in developing the GFP–β3-integrin construct. This study was supported by grants from the Swiss National Science Foundation.
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