The kinetics of force‐induced cell reorganization depend on microtubules and actin

Abstract

The cytoskeleton is an important factor in the functional and structural adaption of cells to mechanical forces. In this study we investigated the impact of microtubules and the acto-myosin machinery on the kinetics of force-induced reorientation of NIH3T3 fibroblasts. These cells were subjected to uniaxial stretching forces that are known to induce cellular reorientation perpendicular to the stretch direction. We found that disruption of filamentous actin using cytochalasin D and latrunculin B as well as an induction of a massive unpolarized actin polymerization by jasplakinolide, inhibited the stretch-induced reorientation. Similarly, blocking of myosin II activity abolished the stretch-induced reorientation of cells but, interestingly, increased their motility under stretching conditions in comparison to myosin-inhibited nonstretched cells. Investigating the contribution of microtubules to the cellular reorientation, we found that, although not playing a significant role in reorientation itself, microtubule stability had a significant impact on the kinetics of this event. Overall, we conclude that acto-myosin, together with microtubules, regulate the kinetics of force-induced cell reorientation. © 2010 Wiley-Liss, Inc.

Disentangling the multifactorial contributions of fibronectin, collagen and cyclic strain on MMP expression and extracellular matrix remodeling by fibroblasts

“…Fn-rich towards collagen-rich might tune fibroblast behavior and specifically their ECM repair and remodeling capacity. We looked into this question by observing HFFs in the presence or absence of uniaxial cyclic strain, since uniaxial cyclic strain is a known inducer of ECM remodeling, resulting in fibroblast reorientation (Dartsch et al, 1986;De et al, 2007;Jungbauer et al, 2008;Faust et al, 2011), cytoskeletal reorganization (Goldyn et al, 2009;Goldyn et al, 2010;Deibler et al, 2011), focal adhesion realignment (Carisey et al, 2013) and altered matrix composition (Gupta and Grande-Allen, 2006;Shelton and Rada, 2007;Kanazawa et al, 2009;Nguyen et al, 2009;Cha and Purslow, 2010;Foolen et al, 2012).…”

Cyclic Tensile Strain Controls Cell Shape and Directs Actin Stress Fiber Formation and Focal Adhesion Alignment in Spreading Cells

“…This tension is proposed to be a key element in cell matrix rigidity sensing, and in responses to extracellular forces or geometries [4], [5], [6], [7], [8], [9], [10]. The assembly of actin stress fiber and their structural arrangement inside of cells also 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]. Therefore, the dynamic formation of the cytoskeleton, especially of the filamentous actin networks including actin stress fibers, is a well-studied phenomenon in cell biology.…”

“…In some studies, adhesive cells are exposed to uniaxial cyclic tensile strain (CTS) applied to the culture substrates. Cells polarize perpendicular with respect to the applied strain and hence reorganize their actin stress fiber system and their adhesion machinery [4], [12], [13], [19], [20], [21], [22]. The actin cytoskeleton has been shown to be essential in the regulation of this stretch-induced cell polarization and plays, together with focal adhesion sites, a key role in this process [6], [9], [12], [23].…”

Featured Article: Temporal responses of human endothelial and smooth muscle cells exposed to uniaxial cyclic tensile strain

“…30,31 Cells adherent on an expandable elastomeric substrate coated with extracellular matrix molecules like fibronectin or collagen can be exposed to a mechanical tensile strain. 32 Several studies have shown that cells on uniaxial cyclically stretched substrates reorient themselves nearly perpendicular to the direction of strain [32][33][34][35][36][37][38][39][40][41] and that the actin cytoskeleton is reorganized perpendicular to the strain direction. [33][34][35]42 Cultured SMCs in vitro can be induced to reorient to a uniform perpendicular alignment into the direction of principal uniaxial mechanical strain.…”

“…32 Several studies have shown that cells on uniaxial cyclically stretched substrates reorient themselves nearly perpendicular to the direction of strain [32][33][34][35][36][37][38][39][40][41] and that the actin cytoskeleton is reorganized perpendicular to the strain direction. [33][34][35]42 Cultured SMCs in vitro can be induced to reorient to a uniform perpendicular alignment into the direction of principal uniaxial mechanical strain. 16,41,43,44 The SMC orientation response is consistent with the response that has been found for many different cell types such as ECs, osteoblasts, fibroblasts, and melanocytes.…”