The differentiation of focal adhesions from focal complexes is dependent on the development of mechanical stress in the actin cytoskeleton. Stress is produced by the interaction of actin with myosin in actin filament bundles. When this interaction is inhibited by drugs that deactivate myosin, focal adhesions disassemble:
Schematic illustration of the dependence of focal adhesion formation and stress fibre on tension in the actin cytoskeleton. Tension is induced via the formation of myosin filaments and their interaction with actin filaments to form contractile bundles. The drawing together of actin filaments promotes the clustering of matrix receptors (integrins) and the accumulation of proteins that make up the focal adhesion complex (modified from Burridge et al., 1997).
A graphic illustration of the dependence of focal adhesion development on stress is provided by the experiment shown in the movie below (Riveline et al., 2001; Kaverina et al., 2002; Small et al., 2002):
Experiment illustrating the development of focal adhesions in response to increased stress. The experiment was performed on a B16 melanoma cell expressing GFP-VASP. VASP labels the tips of the lamellipodium as well as adhesion foci. The cell shown has initially small adhesion foci (focal complexes) behind the broad lamellipodium front. Tension was applied across the cell by pulling back the cell body with a microneedle. Note that this causes the increase in size of adhesions behind the lamellipodium that are diametrically opposed to the direction of cell body displacement (inset region). (From Kaverina et al., 2002).
The increase in size of focal adhesions in response to stress ocurs in parallel with the accumulation of actin filaments within the network of the cell into bundles. This can be illustrated using the same experimental protocol as in the figure below, using a label for actin filaments.
Experiment illustrating the development of actin stress fibre bundles in response to increased stress. A B16 melanoma cell was transfected with GFP-calponin, an actin binding protein that incorporates only into stress fibre bundles (Gimona et al., 2003). In response to stress applied across the cell, by mechanical displacement of the cell body (see movie above), actin filaments from the cytoplasmic network are recruited into bundles, visible as calponin-positive fibres. (From Kaverina et al., 2002)
For reviews see Vasiliev (1985), Burridge and Chrzanowska-Wodnicka (1996) and Geiger et al. (2009).
Related Publications
- Burridge, K., Chrzanowska-Wodnicka, M. (1996). Focal adhesions, contractility, and signaling. Annu Rev Cell Dev Biol. 12:463 — 518.
- Burridge, K., Chrzanowska-Wodnicka, M., Zhong, C. (1997). Focal adhesion assembly. Trends Cell Biol. 7(9): 342 — 347.
- Geiger, B., Spatz, J.,P., Bershadsky, A. D. (2009). Environmental sensing through focal adhesions. Nat. Rev. Mol. Cell Biol. 10 :121–133.
- Gimona, M., Kaverina, I., Resch, G. P., Vignal, E., Burgstaller, G. (2003). Calponin repeats regulate actin filament stability and formation of podosomes in smooth muscle cells. Mol.Biol. Cell. 14, 2482–2491.
- Kaverina, I., Krylyshkina, O., Small, J. V. (2002). Regulation of substrate adhesion dynamics during cell motility. Int. J. Biochem. Cell Biol. 34, 746–61.
- Riveline, D., Zamir E., Balaban, N. Q., Schwarz, S. U., Ishizaki, T., Narumiya, S., Kam, Z., Geiger, B., Bershadsky, A. D. (2001). Focal contacts as mechanosensors: externally applied local mechanical force induces growth of focal contacts by an mDia1-dependent and ROCK-independent mechanism. J. Cell. Biol. 11, 1175–1186.
- Small, J. V., Geiger, B., Kaverina, I., Bershadsky, A. (2002). How do microtubules guide migrating cells? Nat. Rev. Mol. Cell Biol. 3, 957–64.
- Vasiliev, J. M. (1985). Spreading of non-transformed and transformed cells. Biochim Biophys Acta. 780(1): 21 — 65.
