- What are actin filaments
- Actin Filament Polarity
- Distribution of actin filaments in cells and tissues
- Actin Filament Function
- Actin filament polymerization generates protrusive force
- Actin filaments are a force-sensing conduit for both internal and external forces
- Actin filaments form higher-order assemblies that produce and respond to force
* To form the dynamic cytoskeleton, which gives structural support to cells and links the interior of the cell with its surroundings. Forces acting on the actin cytoskeleton are translated and transmitted by signaling pathways to convey information about the external environment.
* In muscle cells, actin filaments are aligned and myosin proteins generate forces on the filaments to support muscle contraction. These complexes are known as 'thin filaments'.
* In non-muscle cells, actin filaments form a track system for cargo transport that is powered by non-conventional myosins such as myosin V and VI. Non-conventional myosins use the energy from ATP hydrolysis to transport cargo (such as vesicles and organelles) at rates much faster than diffusion.
Troponin, a three-peptide complex, is thought to trap tropomyosin in a calcium-dependent fashion at a position that inhibits myosin bundles from accessing the actin filaments; calcium binding to troponin allows a conformational restructuring of tropomyosin that leaves the myosin-binding sites on the thin filaments exposed [22, 23, 24, 25]. Subsequent binding of the myosin thick filaments augments movement of tropomyosin away from the actin filament and full exposure of the myosin binding sites . However, control of tropomyosin-binding to myosin thick filaments may be independent of troponin presence ; smooth muscle cells and many non-muscle cells lack troponin.
In cells, actin filaments are initiated with their barbed ends oriented towards the plasma membrane, with ATP hydrolysis facilitating filament growth. Polymerization is favored towards the cell front and disassembly occurs more frequently at the rear (reviewed in ). However, only a small fraction of the overall free energy of nucleotide hydrolysis is needed to modulate G-actin monomer binding. The remaining energy is translated into a protrusive force that deforms the plasma membrane in a particular direction [40, 41, 42, 43] (reviewed in ).
The propulsive network is self-organizing and filaments with a particular orientation,with respect to the membrane, will assemble at the maximal velocity and be preferentially chosen for elongation . Similarly, cell shape and migration speed is determined by a dynamic steady state that is self-organizing . As actin filaments grow, they remain fixed within the cytoskeletal network (reviewed in ).
47]) or ATP-binding and hydrolysis on actin (reviewed in ) will promote filament assembly and membrane protrusion.
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 membrane protrusion dynamics  (reviewed in [44, 45, 49, 50, 51]).
Membrane tension- In order for a cell to extend its leading edge forward, the cell must overcome resisting forces. Motile cells in living systems experience external forces from the surrounding material (usually ECM), while the major force resisting extension for cells in tissue culture are tensile forces within the plasma membrane. Biophysical models [44, 52, 53] (reviewed in [54, 55]) and experiments with live cells have shown that the membrane extension rate is directly dependent on the membrane tension: elevated tension lowers cell membrane extension and motility, regardless of whether the tension is applied externally (e.g. stretching) or internally (e.g. contraction of stress fibers) [43, 56, 57].
Cells exert traction forces on the ECM and generate tension at focal adhesions through actin stress fibers, which are higher-order structures in the cytoplasm that consist of parallel contractile bundles of actin and myosin filaments. Stress fibers are linked at their ends to the ECM through focal adhesion complexes. Cell tension is generated along the actin filaments by the movement of myosin II motor proteins along the filaments (see contractile bundles). The elasticity of the actin network appears to be inherent to actin filaments and is independent of myosin II motor activity . Forces produced by the contraction of stress fibers not only helps the cell body to translocate during migration [84, 93], but they also serve as a vital “inside-out” feedback system to regulate actin filament initiation , cell growth and motility [95, 96], and formation/maturation of focal adhesion complexes [97, 98]. Forces produced by stress fibers also stabilize the cell structure and contribute to establishing the cell polarity  and they help determine the cell fate [76, 99]. There is no evidence that forces influence stress fiber contractile activity by increasing the exchange of ADP for ATP on myosin, however, force can weakly increase the release of the myosin heads from the actin filaments (reviewed in ).