Vimentin fibers orient traction stress

Abstract

The intermediate filament vimentin is required for cells to transition from the epithelial state to the mesenchymal state and migrate as single cells; however, little is known about the specific role of vimentin in the regulation of mesenchymal migration. Vimentin is known to have a significantly greater ability to resist stress without breaking in vitro compared with actin or microtubules, and also to increase cell elasticity in vivo. Therefore, we hypothesized that the presence of vimentin could support the anisotropic mechanical strain of single-cell migration. To study this, we fluorescently labeled vimentin with an mEmerald tag using TALEN genome editing. We observed vimentin architecture in migrating human foreskin fibroblasts and found that network organization varied from long, linear bundles, or "fibers," to shorter fragments with a mesh-like organization. We developed image analysis tools employing steerable filtering and iterative graph matching to characterize the fibers embedded in the surrounding mesh. Vimentin fibers were aligned with fibroblast branching and migration direction. The presence of the vimentin network was correlated with 10-fold slower local actin retrograde flow rates, as well as spatial homogenization of actin-based forces transmitted to the substrate. Vimentin fibers coaligned with and were required for the anisotropic orientation of traction stresses. These results indicate that the vimentin network acts as a load-bearing superstructure capable of integrating and reorienting actin-based forces. We propose that vimentin's role in cell motility is to govern the alignment of traction stresses that permit single-cell migration.

Vimentin provides the mechanical resilience required for amoeboid migration and protection of the nucleus

“…Cells that are pliable, spongy, and yielding, as vimentin-deficient cells will be, are not likely to be able to efficiently generate such forces. This outset for suspension cells is compatible with previous reports regarding adhesive cells, concluding that vimentin IFs serve as a load-bearing scaffold to shield traction stress during single-cell migration [4]. In this study, in the presence of vimentin, actomyosin-dependent traction forces were redirected to peripheral adhesions, which also fits with the concept we are presenting for suspension cells.…”

“…Vimentin is the major IF protein in a broad variety of cell types, especially in motile and dynamic cells of mesenchymal origin. In this regard, vimentin has been implicated to be involved in different migratory functions of a number of different adherent cell types, especially in relation to the organization and functionalities of actomyosin complexes [2][3][4]. The role of vimentin in cell migration has been primarily addressed in adherent cells [5].…”

Condensed desmin and actin cytoskeletal communication in lipid droplets

“…During the migration of mesenchymal cells, IFs align and orient toward the leading edges (Costigliola et al, 2017). This arrangement is controlled by their interaction with actin filaments and microtubules via cross-linking proteins, such as plectin (Leduc & Etienne-Manneville, 2015).…”

Hypotonic stress induces fast, reversible degradation of the vimentin cytoskeleton via intracellular calcium release

“…Vimentin is a major component of the intermediate filament system for most cells in culture (Lazarides, 1982); besides supporting the cell shape, it also anchors organelles and impedes intracellular movement by doubling the cytoplasmic shear modulus (Guo et al, 2013;Lowery et al, 2015;Robert et al, 2016). Recent work underscores the dynamic interplays between the vimentin system and the actin and tubulin cytoskeletal systems (Costigliola et al, 2017;Gan et al, 2016;Hookway et al, 2015;Jiu et al, 2015). One emerging theme has been that the vimentin system follows the initial structural cues of the more dynamic actin and tubulin systems, but subsequently helps provide structural persistency through its superior stability and rigidity.…”