skip to main content
US FlagAn official website of the United States government
dot gov icon
Official websites use .gov
A .gov website belongs to an official government organization in the United States.
https lock icon
Secure .gov websites use HTTPS
A lock ( lock ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Explore Research Products in the PAR
It may take a few hours for recently added research products to appear in PAR search results.


Title: Influence of the vessel wall geometry on the wall-induced migration of red blood cells
The geometry of the blood vessel wall plays a regulatory role on the motion of red blood cells (RBCs). The overall topography of the vessel wall depends on many features, among which the endothelial lining of the endothelial surface layer (ESL) is an important one. The endothelial lining of vessel walls presents a large surface area for exchanging materials between blood and tissues. The ESL plays a critical role in regulating vascular permeability, hindering leukocyte adhesion as well as inhibiting coagulation during inflammation. Changes in the ESL structure are believed to cause vascular hyperpermeability and entrap immune cells during sepsis, which could significantly alter the vessel wall geometry and disturb interactions between RBCs and the vessel wall, including the wall-induced migration of RBCs and the thickening of a cell-free layer. To investigate the influence of the vessel wall geometry particularly changed by the ESL under various pathological conditions, such as sepsis, on the motion of RBCs, we developed two models to represent the ESL using the immersed boundary method in two dimensions. In particular, we used simulations to study how the lift force and drag force on a RBC near the vessel wall vary with different wall thickness, spatial variation, and permeability associated with changes in the vessel wall geometry. We find that the spatial variation of the wall has a significant effect on the wall-induced migration of the RBC for a high permeability, and that the wall-induced migration is significantly inhibited as the vessel diameter is increased.  more » « less
Award ID(s):
1913093
PAR ID:
10439361
Author(s) / Creator(s):
;
Editor(s):
Beard, Daniel A
Date Published:
Journal Name:
PLOS Computational Biology
Volume:
19
Issue:
7
ISSN:
1553-7358
Page Range / eLocation ID:
e1011241
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. ; ; ; ; ; ; ; ; ; ; et al (, Blood)
    AbstractSickle cell disease (SCD) is canonically characterized by reduced red blood cell (RBC) deformability, leading to microvascular obstruction and inflammation. Although the biophysical properties of sickle RBCs are known to influence SCD vasculopathy, the contribution of poor RBC deformability to endothelial dysfunction has yet to be fully explored. Leveraging interrelated in vitro and in silico approaches, we introduce a new paradigm of SCD vasculopathy in which poorly deformable sickle RBCs directly cause endothelial dysfunction via mechanotransduction, during which endothelial cells sense and pathophysiologically respond to aberrant physical forces independently of microvascular obstruction, adhesion, or hemolysis. We demonstrate that perfusion of sickle RBCs or pharmacologically-dehydrated healthy RBCs into small venule-sized “endothelialized” microfluidics leads to pathologic physical interactions with endothelial cells that directly induce inflammatory pathways. Using a combination of computational simulations and large venule-sized endothelialized microfluidics, we observed that perfusion of heterogeneous sickle RBC subpopulations with varying deformability, as well as suspensions of dehydrated normal RBCs admixed with normal RBCs, leads to aberrant margination of the less-deformable RBC subpopulations toward the vessel walls, causing localized, increased shear stress. Increased wall stress is dependent on the degree of subpopulation heterogeneity and oxygen tension and leads to inflammatory endothelial gene expression via mechanotransductive pathways. Our multifaceted approach demonstrates that the presence of sickle RBCs with reduced deformability leads directly to pathological physical (ie, direct collisions and/or compressive forces) and shear-mediated interactions with endothelial cells and induces an inflammatory response, thereby elucidating the ubiquity of vascular dysfunction in SCD. 
    more » « less
  2. ; ; ; (, Science Advances)
    Red blood cell (RBC) disorders such as sickle cell disease affect billions worldwide. While much attention focuses on altered properties of aberrant RBCs and corresponding hemodynamic changes, RBC disorders are also associated with vascular dysfunction, whose origin remains unclear and which provoke severe consequences including stroke. Little research has explored whether biophysical alterations of RBCs affect vascular function. We use a detailed computational model of blood that enables characterization of cell distributions and vascular stresses in blood disorders and compare simulation results with experimental observations. Aberrant RBCs, with their smaller size and higher stiffness, concentrate near vessel walls (marginate) because of contrasts in physical properties relative to normal cells. In a curved channel exemplifying the geometric complexity of the microcirculation, these cells distribute heterogeneously, indicating the importance of geometry. Marginated cells generate large transient stress fluctuations on vessel walls, indicating a mechanism for the observed vascular inflammation. 
    more » « less
  3. ; ; ; ; ; (, Function)
    Abstract The wall shear stress (WSS) exerted by blood flowing through microvascular capillaries is an established driver of new blood vessel growth, or angiogenesis. Such adaptations are central to many physiological processes in both health and disease, yet three-dimensional (3D) WSS characteristics in real angiogenic microvascular networks are largely unknown. This marks a major knowledge gap because angiogenesis, naturally, is a 3D process. To advance current understanding, we model 3D red blood cells (RBCs) flowing through rat angiogenic microvascular networks using state-of-the-art simulation. The high-resolution fluid dynamics reveal 3D WSS patterns occurring at sub-endothelial cell (EC) scales that derive from distinct angiogenic morphologies, including microvascular loops and vessel tortuosity. We identify the existence of WSS hot and cold spots caused by angiogenic surface shapes and RBCs, and notably enhancement of low WSS regions by RBCs. Spatiotemporal characteristics further reveal how fluctuations follow timescales of RBC “footprints.” Altogether, this work provides a new conceptual framework for understanding how shear stress might regulate EC dynamics in vivo. 
    more » « less
  4. ; ; ; ; (, Summer Biomechanics, Bioengineering, and Biotransport Conference (SB3C))
    The endothelium, composed of a single layer of endothelial cells, is the innermost lining of vessels, acting as the interface between blood and the arterial wall. “Endothelial dysfunction” is defined as reduction or loss of bioavailability of endothelial-derived nitric oxide (NO), a condition that precedes or accompanies several cardiovascular pathologies associated with aging, such as atherosclerosis. [1] [2] NO plays an important role in regulating vascular tone and maintaining vascular homeostasis as a vasodilator. Thus, we hypothesize that decreased NO production may induce collagen fiber reorientation and increased collagen production, to shift load from smooth muscle cells to the extracellular matrix, eventually leading to vascular remodeling. The aim of this project is to study the impact of NO deficiency on hemodynamic parameters, collagen content, and collagen fiber orientation during age-related vascular remodeling using a mouse model. 
    more » « less
  5. ; ; ; ; (, Microcirculation)
    ABSTRACT ObjectiveTortuous microvessels are characteristic of microvascular remodeling associated with numerous physiological and pathological scenarios. Three‐dimensional (3D) hemodynamics in tortuous microvessels influenced by red blood cells (RBCs), however, are largely unknown, and important questions remain. Is blood viscosity influenced by vessel tortuosity? How do RBC dynamics affect wall shear stress (WSS) patterns and the near‐wall cell‐free layer (CFL) over a range of conditions? The objective of this work was to parameterize hemodynamic characteristics unique to a tortuous microvessel. MethodsRBC‐resolved simulations were performed using an immersed boundary method‐based 3D fluid dynamics solver. A representative tortuous microvessel was selected from a stimulated angiogenic network obtained from imaging of the rat mesentery and digitally reconstructed for the simulations. The representative microvessel was a venule with a diameter of approximately 20 μm. The model assumes a constant diameter along the vessel length and does not consider variations due to endothelial cell shapes or the endothelial surface layer. ResultsMicrovessel tortuosity was observed to increase blood apparent viscosity compared to a straight tube by up to 26%. WSS spatial variations in high curvature regions reached 23.6 dyne/cm2over the vessel cross‐section. The magnitudes of WSS and CFL thickness variations due to tortuosity were strongly influenced by shear rate and negligibly influenced by tube hematocrit levels. ConclusionsNew findings from this work reveal unique tortuosity‐dependent hemodynamic characteristics over a range of conditions. The results provide new thought‐provoking information to better understand the contribution of tortuous vessels in physiological and pathological processes and help improve reduced‐order models. 
    more » « less
  • Citation Formats
  • MLA
  • APA
  • Chicago
  • BibTeX
  • Save / Share this Record
  • Send to Email