Tension-dependent actin polymerization and assembly of stress fibers is influenced by many factors (reviewed in ), including differences in substrate composition , rigidity  (reviewed in ), cell membrane phospholipids , external force (reviewed in ), as well as by strength of the connection(s) between actin filaments and the adhesion  (reviewed in ).
Each of these cues converges at the level of the Rho family of GTPases and their effector substrates (reviewed in ). The activity of the Rho GTPases is finely regulated by GTPase activating proteins (GAPs), guanine nucleotide exchange factors (GEFs), and guanine nucleotide dissociation inhibitors (GDIs)  (reviewed in ); however, actin-associated proteins such as synaptopodin can also block the degradation of RhoA and lead to stress fiber formation .
Stress fibers function to counter membrane tension and to keep the non-adherent regions of a cell straight . Accordingly, the rate of actin assembly at the leading edge is directly dependent on the membrane tension: elevated tension lowers membrane protrusion and cell motility, regardless of whether the tension is applied externally (e.g., stretching) or internally (e.g., contraction of stress fibers) . Furthermore, Rho GTPases recruit formins to initiate actin assembly from focal adhesions in a manner that is also force-dependent .
As tension regulates the dynamic assembly and disassembly of actin filaments , proteins that contribute to the structural integrity of the filaments will influence the physical transmission of forces across the network. α-actinin and filamin are enriched in arcs and stress fibers  and they are both known to alter the structural dynamics of the actin cytoskeleton (reviewed in ). α-actinin recruits proteins that are important for mechanosensing in stress fibers (e.g., zyxin ) and for stress fiber maintenance (e.g., CLP-36 , palladin ) whereas filamin links the filaments to cellular membranes and its degradation products may act as signaling molecules (reviewed in ). Interestingly, the association of α-actinin with actin filaments and stress fibers is highly dynamic  and dynamic binding is essential for proper cell function ; this implies that any factors that manipulate the actin-binding properties of α-actinin or its association with actin filaments (e.g., Alix ; RIL ) will likely influence the formation of stress fibers.
Membrane curvature, cross-linking and bundling of F-actin at the leading cell edge is mediated by proteins containing IM/I-BAR domains such as IRSp53 (reviewed in ); these proteins interact with actin-associated proteins (e.g., synaptopodin) and components of the actin polymerizing module (e.g., Mena, WAVE) to regulate the protrusive dynamics and structure of the growing actin network . The relative expression level of IRSp53 influences stress fiber assembly: stress fibers are seen when IRSp53 levels are low, while overexpression causes their complete disassembly .
The microtubule and intermediate filament networks play a key role in regulating the global deposition pattern of the actin filaments; therefore, they will also influence actin filament production and membrane protrusion dynamics  (reviewed in ).
- What is the cytoskeleton?
- What are actin filaments?
- What are microtubules?
- What are intermediate filaments?
- What are stress fibers?
- What is the function of stress fibers?
- What are the steps in dorsal stress fiber formation?
- What are the steps in the formation of transverse arcs?
- What are the steps in ventral stress fiber formation?
- How do the mechanical properties of cells change with respect to substrate rigidity?steve2018-02-19T11:09:32+08:30
How do the mechanical properties of cells change with respect to substrate rigidity?
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