title: The influence of matrix integrity on stress-fiber remodeling in 3D.
abstract: Matrix anisotropy is important for long term in vivo functionality. However, it is not fully understood how to guide matrix anisotropy in vitro. Experiments suggest actin-mediated cell traction contributes. Although F-actin in 2D displays a stretch-avoidance response, 3D data are lacking. We questioned how cyclic stretch influences F-actin and collagen orientation in 3D. Small-scale cell-populated fibrous tissues were statically constrained and/or cyclically stretched with or without biochemical agents. A rectangular array of silicone posts attached to flexible membranes constrained a mixture of cells, collagen I and matrigel. F-actin orientation was quantified using fiber-tracking software, fitted using a bi-model distribution function. F-actin was biaxially distributed with static constraint. Surprisingly, uniaxial cyclic stretch, only induced a strong stretch-avoidance response (alignment perpendicular to stretching) at tissue surfaces and not in the core. Surface alignment was absent when a ROCK-inhibitor was added, but also when tissues were only statically constrained. Stretch-avoidance was also observed in the tissue core upon MMP1-induced matrix perturbation. Further, a strong stretch-avoidance response was obtained for F-actin and collagen, for immediate cyclic stretching, i.e. stretching before polymerization of the collagen. Results suggest that F-actin stress-fibers avoid cyclic stretch in 3D, unless collagen contact guidance dictates otherwise.
authors: Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands. J.Foolen@tue.nl
authors: Jasper
authors: J
authors: Foolen
authors: Vikram S
authors: VS
authors: Deshpande
authors: Frans M W
authors: FM
authors: Kanters
authors: Frank P T
authors: FP
authors: Baaijens
mesh_terms: D003094:Collagen / Q000737:chemistry; D005109:Extracellular Matrix / Q000378:metabolism*; D006801:Humans; D021621:Imaging, Three-Dimensional / Q000379:methods*; D022502:Stress Fibers / Q000378:metabolism*; D013314:Stress, Mechanical
chemical_list: D003094:Collagen