Abstract
The actin cytoskeleton plays a crucial role for the spreading of cells, but is also a key element for the structural integrity and internal tension in cells. In fact, adhesive cells and their actin stress fiber–adhesion system show a remarkable reorganization and adaptation when subjected to external mechanical forces. Less is known about how mechanical forces alter the spreading of cells and the development of the actin–cell-matrix adhesion apparatus. We investigated these processes in fibroblasts, exposed to uniaxial cyclic tensile strain (CTS) and demonstrate that initial cell spreading is stretch-independent while it is directed by the mechanical signals in a later phase. The total temporal spreading characteristic was not changed and cell protrusions are initially formed uniformly around the cells. Analyzing the actin network, we observed that during the first phase the cells developed a circumferential arc-like actin network, not affected by the CTS. In the following orientation phase the cells elongated perpendicular to the stretch direction. This occurred simultaneously with the de novo formation of perpendicular mainly ventral actin stress fibers and concurrent realignment of cell-matrix adhesions during their maturation. The stretch-induced perpendicular cell elongation is microtubule-independent but myosin II-dependent. In summary, a CTS-induced cell orientation of spreading cells correlates temporary with the development of the acto-myosin system as well as contact to the underlying substrate by cell-matrix adhesions.
Highlights
The actin cytoskeleton of a cell is a dynamic, adaptive and functional entity ensuring its structural and mechanical integrity
The assembly of actin stress fiber and their structural arrangement inside of cells depends on the matrix rigidity and external forces [4,11,12,13] and it is suggested that several cellular functions, like the differentiation of stem cells are influenced by the architecture of the cytoskeleton [6,14,15]
With beginning of the second phase (‘‘Polarization/Orientation’’), the cell adhesive area reaches its maximum, cell protrusions form preferentially perpendicular to the direction of stretch, and cell elongation is initiated perpendicular to the stretch axis
Summary
The actin cytoskeleton of a cell is a dynamic, adaptive and functional entity ensuring its structural and mechanical integrity. For example, build by actin, myosin IIa and other cross-linkers generate tension forces on focal adhesions by which they are anchored to the extracellular matrix surrounding the cell [1,2,3,4]. Upon contact with an adhesive surface, adhesion-dependent cells start to flatten (spread) within hours.They form adhesive contact sites, actin stress fibers and show tension-dependent changes in cell shape such as the polarization of the cell [17,18]. It is suggested that cells adhering on compliant substrates, spread less and show a more condensed actin stress fiber system than cells on stiffer substrates [10] It is not well understood how external forces affect the assembly of the cytoskeleton during cell spreading
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