title: Temporal responses of human endothelial and smooth muscle cells exposed to uniaxial cyclic tensile strain.
abstract: The physiology of vascular cells depends on stimulating mechanical forces caused by pulsatile flow. Thus, mechano-transduction processes and responses of primary human endothelial cells (ECs) and smooth muscle cells (SMCs) have been studied to reveal cell-type specific differences which may contribute to vascular tissue integrity. Here, we investigate the dynamic reorientation response of ECs and SMCs cultured on elastic membranes over a range of stretch frequencies from 0.01 to 1 Hz. ECs and SMCs show different cell shape adaptation responses (reorientation) dependent on the frequency. ECs reveal a specific threshold frequency (0.01 Hz) below which no responses is detectable while the threshold frequency for SMCs could not be determined and is speculated to be above 1 Hz. Interestingly, the reorganization of the actin cytoskeleton and focal adhesions system, as well as changes in the focal adhesion area, can be observed for both cell types and is dependent on the frequency. RhoA and Rac1 activities are increased for ECs but not for SMCs upon application of a uniaxial cyclic tensile strain. Analysis of membrane protrusions revealed that the spatial protrusion activity of ECs and SMCs is independent of the application of a uniaxial cyclic tensile strain of 1 Hz while the total number of protrusions is increased for ECs only. Our study indicates differences in the reorientation response and the reaction times of the two cell types in dependence of the stretching frequency, with matching data for actin cytoskeleton, focal adhesion realignment, RhoA/Rac1 activities, and membrane protrusion activity. These are promising results which may allow cell-type specific activation of vascular cells by frequency-selective mechanical stretching. This specific activation of different vascular cell types might be helpful in improving strategies in regenerative medicine.
authors: Department of Cell- and Neurobiology, Karlsruhe Institute of Technology (KIT), 76131 Karlsruhe, Germany.
authors: Alexandra M
authors: AM
authors: Greiner
authors: Department of New Materials and Biosystems, Max Planck Institute for Intelligent Systems, 70569 Stuttgart, Germany.
authors: Sarah A
authors: SA
authors: Biela
authors: Department of Cell- and Neurobiology, Karlsruhe Institute of Technology (KIT), 76131 Karlsruhe, Germany.
authors: Hao
authors: H
authors: Chen
authors: Department of New Materials and Biosystems, Max Planck Institute for Intelligent Systems, 70569 Stuttgart, Germany Department of Biophysical Chemistry, University of Heidelberg, 69120 Heidelberg, Germany.
authors: Joachim P
authors: JP
authors: Spatz
authors: Department of New Materials and Biosystems, Max Planck Institute for Intelligent Systems, 70569 Stuttgart, Germany Department of Applied Chemistry, Reutlingen University, 72762 Reutlingen, Germany ralf.kemkemer@reutlingen-university.de.
authors: Ralf
authors: R
authors: Kemkemer
mesh_terms: D008841:Actin Cytoskeleton / Q000502:physiology; D048430:Cell Shape; D042783:Endothelial Cells / Q000166:cytology / Q000502:physiology*; D022001:Focal Adhesions; D006801:Humans; D040542:Mechanotransduction, Cellular; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000502:physiology*; D011673:Pulsatile Flow; D013718:Tensile Strength; D020830:rac1 GTP-Binding Protein / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
chemical_list: D020830:rac1 GTP-Binding Protein; D020742:rhoA GTP-Binding Protein
keywords: Rho GTPases; Smooth muscle cell; actin; endothelial cell; focal adhesion; uniaxial cyclic tensile strain