Abstract
The glycocalyx has been identified as a key mechano-sensor of the shear forces exerted by streaming blood onto the vascular endothelial lining. Although the biochemical reaction to the blood flow has been extensively studied, the mechanism of transmission of the haemodynamic shear forces to the endothelial transmembrane anchoring structures and, consequently, to the subcellular elements in the cytoskeleton, is still not fully understood. Here we apply a multiscale approach to elucidate how haemodynamic shear forces are transmitted to the transmembrane anchors of endothelial cells. Wall shear stress time histories, as obtained from image-based computational haemodynamics models of a carotid bifurcation, are used as a load and a continuum model is applied to obtain the mechanical response of the glycocalyx all along the cardiac cycle. The main findings of this in silico study are that: (1) the forces transmitted to the transmembrane anchors are in the range of 1–10 pN, which is in the order of magnitude reported for the different conformational states of transmembrane mechanotranductors; (2) locally, the forces transmitted to the anchors of the glycocalyx structure can be markedly different from the near-wall haemodynamic shear forces both in amplitude and frequency content. The findings of this in silico approach warrant future studies focusing on the actual forces transmitted to the transmembrane mechanotransductors, which might outperform haemodynamic descriptors of disturbed shear as localizing factors of vascular disease.
Highlights
There is clear evidence that endothelial cells (ECs) respond to shear forces with a variety of mechanotransduction processes that lead to biophysical, biochemical and gene regulatory changes [1,2,3,4], with important implications in terms of cardiovascular pathologies [5,6,7,8]
It can be observed that high oscillatory shear index (OSI) values and low time averaged wall shear stress (TAWSS) values are both localized at the carotid bulb, in accordance with previous reports [34]
These regions are characterized by a low magnitude and rapid changes in the orientation of the WSS vector compared with the proximal region of the common carotid artery (CCA), and the distal regions of internal carotid artery (ICA) and external carotid artery (ECA) [34,36,51]
Summary
There is clear evidence that endothelial cells (ECs) respond to shear forces with a variety of mechanotransduction processes that lead to biophysical, biochemical and gene regulatory changes [1,2,3,4], with important implications in terms of cardiovascular pathologies [5,6,7,8]. The GCX, a conglomerate of proteins and macromolecules lining the apical side of the ECs membrane, exhibits a very distinctive response to external stimuli, i.e. highly dynamic fluid forces, which are not present in any other cell type How these mechanical forces are transmitted from the streaming blood to the anchoring elements at the GCX is still poorly understood [11,14,15]. A multiscale approach is applied to explore how haemodynamic shear forces are transmitted to the transmembrane anchors of ECs via the mechanical response of the GCX layer For such a purpose, haemodynamic shear force time histories were first obtained through image-based computational haemodynamic modelling at the luminal surface of a carotid bifurcation, a vascular district prone to atherosclerotic lesion development. The dynamic forces transduced to the anchoring elements of the HS on the EC membrane are evaluated and compared to the haemodynamic shear forces
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