Stress fiber

Stress fibers are necessary for the formation and maintenance of cell-cell and cell-ECM adhesion, such as the formation of adherens junctions, tight junctions and focal adhesions.[9][10]

Adherens junctions are a type of cell-cell adhesion structure that is present in both motile and non-motile cells, which adhere cells together via the homophilic binding of cadherins and nexins.[11] Stress fibers play an important role in the maintenance of cadherin-dependent and nexin-dependent cell-cell contacts,[12] and the Rho-family GTPases have been found to regulate the structure and integrity of adherens junctions.[13] α-catenin and β-catenin are integral components of adherens junctions, which bind together to produce cadherin-α-catenin-β-catenin complexes.[14] Early studies showed that α-catenin could interact with actin filaments, leading to the belief that α-catenin links the actin cytoskeleton to adherens junctions.[15] However it was later found that α-catenin can only bind F-actin when it is unbound by β-catenin and cadherin.[16]

Recently, α-catenin has been shown to associate with formins,[17] EPLIN, and vinculin. EPLIN has been found to enhance the bundling and stabilization of actin filaments,[18] and vinculin is involved in the linkage of adhesion molecules to the actin cytoskeleton. This may serve as a mechanism for how actin is recruited to adherens junctions.[19]

Tight junctions, or zona occludens, are the most important cellular element for the formation of semi-permeable barriers within or between tissues.[20] Tight junctions primarily consist of claudins and occludins, which are membrane proteins that form the cell-cell contact, as well as ZO-1, ZO-2 and ZO-3, which link tight junctions to the actin cytoskeleton.[21] However, tight junctions have not been found to be directly linked to stress fibers, like they are for focal adhesions and adherens junctions.

Focal adhesions are macromolecular assemblies that are used to connect cells to the ECM. They consist of three functional layers: an ECM-associated integrin layer, a membrane associated force transduction layer, and an actin layer, which is made up of actin stress fibers.[22] As the naming or their layers implies, focal adhesions play a large role in mechanotransduction and cell migration. Focal adhesions are usually connected to stress fibers—in fact, stress fiber contractility is necessary for focal adhesion maintenance.[23]

Three types of stress fibers: ventral stress fibers, transverse arcs, and dorsal stress fibers

An essential feature of many cells is their ability to migrate towards certain mechanical (Durotaxis) or chemical (Chemotaxis) stimuli.[24] Cell migration takes place through the concerted action of three Rho family GTPases: Rho, Rac, and Cdc42. When GTP-bound, Rac will cause the formation of lamellipodia, and Cdc42 will cause the formation of filopodia, thus promoting cell migration. In the migrating cell, there are three main types of stress fibers: ventral stress fibers, transverse arcs, and dorsal stress fibers.[25] Ventral stress fibers are associated with focal adhesions at both ends, are located on the ventral surface of the cell, and function in adhesion and contraction.[26] Transverse arcs are not directly linked to focal adhesions, and typically flow from the leading edge of the cell, back towards the cell centre.[27] Dorsal stress fibers are located at the leading edge of the cell. They attach to focal adhesions on the ventral surface of the leading edge, and extend dorsally, towards the cell centre to attach to transverse arcs.[28] During cell migration, actin filaments within stress fibers will be recycled by a process of retrograde actin flow. The mechanism of dissolution of the focal adhesion itself is poorly understood.

Morphogenesis, at the cellular level, can be defined as giving shape to, or defining the architecture of a cell. The assembly of the cytoskeleton, including the actin cytoskeleton, is the determining factor in specifying cellular morphogenesis and conferring shape to cells. The contractility of stress fibers within the cell will therefore help to determine cellular morphogenesis. For example, the circumferential contractile actin belts of adherens junctions contribute to cellular morphogenesis.[29] As well, the dorsal stress fibers, transverse arcs and ventral stress fibers aid in the determination of cell morphology during cell migration. A more detailed explanation of cellular morphogenesis can be found here.

Both microfilaments and microtubules play major roles in mechanotransduction. In the actin cytoskeleton, mechanotransduction can occur at cell-ECM and cell-cell adhesions, through focal adhesions and adherens junctions, respectively.[30] Transduction of forces from the outside to the inside of the cell can control the maturation or disassembly of adhesions, and initiate intracellular signalling cascades that can alter cellular behaviours,[31] and cells are known to assemble stress fibers when they encounter mechanical stress.[32] For example, cells that are grown on rigid substrates will show thick stress fibers, whereas the stress fibers seen in cells grown on softer substrates will be less pronounced.[33] The mechanical force transmitted to focal adhesions by stress fibers can also alter the conformation of mechanosensitive focal adhesion proteins, such as p130Cas[34] and talins,[35] suggesting that stress fiber contractility may translate mechanical signals into biochemical cues. There are also a small subset of focal adhesion-associated integrins that terminate in the perinuclear actin cap (at the top of the nucleus), and are anchored there by the LINC complex.[36] These cap-associated focal adhesions have been established as major mediators in mechanosensing, and represent a direct pathway for the transduction of mechanical cues from focal adhesions to the nucleus.[37]