Adhesions that manage to grow beyond the transient phase further undergo qualitative changes in a phase described as maturation. This transformation of adhesion sites into stress-fiber bound focal adhesions (FAs) is believed to result from the collective effects of Rho GTPase activity , increased tyrosine kinase activity  (reviewed in ), change in composition  and dynamics , actin crosslinking by α-actinin and tension-dependent actomyosin contractility (, reviewed in ) – all of which take place during local contraction of the lamellipodium  (reviewed in ).
Rho kinase (ROCK)-mediated phosphorylation of myosinII regulatory light chain (RLC), RhoA-mediated its sustenance of RLC phosphorylation and activation of formin mDia are critical triggering events . For more details, see Functional module: Integrin β1/syndecan-4 synergy in membrane protrusion and adhesion dynamics. Myosin IIA and Myosin IIB cooperatively aid actomyosin bundling in a localized manner thus stabilizing the large adhesions . As a result, actin bundles assemble between stable adhesions on the ventral cell surface, forming structures known as stress fibers (, reviewed in ). Assembly of these stress fibers in the lamellum acts as a structural template for the compositional maturation of FAs and seems to be quintessential despite an intact actomyosin contractile mechanism . At this stage, the adhesion components contain modifications that inhibit Rac-GEF recruitment leading to a local and hence define the cell rear . Stress fibers participate in mechanotransduction by FAs  and can generate high level of forces on rigid and dense matrices , through actomyosin contractions.
Accumulation of tensional forces (internal or external) that results in FA reinforcement has been shown to ultimately activate and recruit Rho-GEFs to adhesion sites . The two GEFs studied seem to be under the control of distinct pathways- Fyn (a SFK) and FAK-Ras-ERK signaling. Subsequent force-dependent Rho activation leads to events aiding the maturation process.
Thus, bidirectional force transmission between the internal cytoskeletal network and the exterior gets directed through the adhesions  (reviewed in ). Force differences across adhesions influence actin dynamics and signal transduction cascades, leading to the reinforcement and maturation of adhesions (reviewed in ).
During growth and early maturation, the FA size correlates with traction stress but can exert variable force depending on its position in the cell . However, upon maturation, the changes in morphology, protein composition and/or phosphorylation of FAs decrease propulsive forces . They do not grow further under tension  probably due to altered chemical state of FA signaling components .
Thus mature FAs effectively become passive anchorage devices for the maintenance of a spread cell morphology  and can sustain up to a six-fold increase in external force load without elongating . Stability of receptor-stress fiber interactions enables mature adhesions to probe their environment over large spatial and temporal scales and to reorient, a feature essential for direction-dependent rigidity sensing .
FAs typically disassemble within 10 to 20 minutes or mature further into fibrillar adhesions  that can remodel the extracellular matrix. Alternately, high Src activity suppresses integrin function and contractility, thus fail to assemble the matrix and mediate transformation into podosomes .
- What are focal adhesions?
- How are focal adhesion dynamics regulated?
- What steps are involved in the formation of focal adhesions?
- What is the first step in focal adhesion assembly?
- What are mature focal adhesions composed of?
- How do focal adhesions disassemble?
- What is actomyosin?
- What are stress fibers?
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