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. 12:463518. NCBI PubMed
  • Bur­ridge, K., Chrzanowska-Wodnicka, M., Zhong, C. (1997). Focal adhe­sion assem­bly. Trends Cell Biol. 7(9): 342347. NCBI PubMed
  • Geiger, B., Spatz, J.,P., Ber­shad­sky, A. D. (2009). Envi­ron­men­tal sens­ing through focal adhe­sions. Nat. Rev. Mol. Cell Biol. 10 :121133. NCBI PubMed
  • 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, 24822491. NCBI PubMed
  • Kave­rina, I., Krylyshk­ina, O., Small, J. V. (2002). Reg­u­la­tion of sub­strate adhe­sion dynam­ics dur­ing cell motil­ity. Int. J. Biochem. Cell Biol. 34, 74661. PDF
  • 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, 11751186. NCBI PubMed
  • Small, J. V., Geiger, B., Kave­rina, I., Ber­shad­sky, A. (2002). How do micro­tubules guide migrat­ing cells? Nat. Rev. Mol. Cell Biol. 3, 95764. PDF
  • Vasiliev, J. M. (1985). Spread­ing of non-transformed and trans­formed cells. Biochim Bio­phys Acta. 780(1): 2165. NCBI PubMed

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