Featured Article: 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.

Endothelial Plasticity: Shifting Phenotypes through Force Feedback

“…The activity of the Rho pathway determines the direction and extent of stretch-induced stress fiber orientation in endothelial cells. This demonstrates on one hand that physically stressing a cell determines Rho activity (in a linear fashion) and that Rho activation directly correlates with physical shape shifting of cells through cytoskeletal reorganization [ 140 , 141 ]. Also, preconditioning of endothelial cells at 18% CS enhanced the effects of prothrombotic stimuli to induce permeability of the endothelial monolayer, while 5% CS prevents thrombin-induced disruptive response and accelerates barrier recovery [ 142 ].…”

“…EndMT results in a loss of barrier function, that is, increased permeability, which correlates with loss of VE-Cadherin at the cell surface ( Figure 4 ). In response to the increase of Rho activity by high levels of CS [ 141 ], VE-Cadherin is translocated from the membrane into the cytoplasm. The concomitant loss of complexed β -catenin and its nuclear translocation might therefore be a secondary mediator of EndMT.…”

In SilicoTissue Engineering: A Coupled Agent-Based Finite Element Approach

“…38 According to the phenomenon, known as stretch avoidance response, 39 SMCs and other cell types align perpendicular to the direction of uniaxial cyclic mechanical stretch. [40][41][42][43] The extent of alignment is dependent on the frequency, 41,44 amplitude, 37,41 and duration of the stretch. 45,46 It is important to note that the impact of topographic cues was not considered in this model, and the results may differ for vascular grafts that contain these cues.…”

Nano- and microstructured materials for in vitro studies of the physiology of vascular cells

“…The surface (bio)chemistry of a material may regulate cell adhesion, survival, proliferation and differentiation of vascular cells or progenitor cells [10,31,126,128–131]. In order to make a biological meaningful contact with a surface, cellular trans-membrane adhesion molecules such as integrins need to interact with specific counterparts, generally ligand molecules of the extracellular matrix or molecules with similar motifs [132–136].…”