Abstract
The flow patterns of red blood cells through the spleen are intimately linked to clearance of senescent RBCs, with clearance principally occurring within the open flow through the red pulp and slits of the venous sinus system that exists in humans, rats, and dogs. Passage through interendothelial slits (IESs) of the sinus has been shown by MacDonald et al. (Microvasc Res 33:118–134, 1987) to be mediated by the caliber, i.e., slit opening width, of these slits. IES caliber within a given slit of a given sinus section has been shown to operate in an asynchronous manner. Here, we describe a model and simulation results that demonstrate how the supporting forces exerted on the sinus by the reticular meshwork of the red pulp, combined with asymmetrical contractility of stress fibers within the endothelial cells comprising the sinus, describe this vital and intriguing behavior. These results shed light on the function of the sinus slits in species such as humans, rats, and dogs that possess sinusoidal sinuses. Instead of assuming a passive mechanical filtering mechanism of the IESs, our proposed model provides a mechanically consistent explanation for the dynamically modulated IES opening/filtering mechanism observed in vivo. The overall perspective provided is also consistent with the view that IES passage serves as a self-protective mechanism in RBC vesiculation and inclusion removal.
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M.D. acknowledges support from NIH R01HL154150.
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R.J. Asaro, M. Dao, and I. MacDonald all contributed to and performed the research and the writing of this paper.
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Deformation of a sinus section under the conditions of Model 1 with the endothelial cell (EC) modulus taken as 10 kPa and LEC = 16 μm. The evolution of the longitudinal strain along the ECs (ε LEC = LE33) is shown first under Ppull = 0 - 0.5 mmHg (0 - 66.7 Pa) with no stress fiber contraction, followed by adding 0 to 20% uniform stress fiber contraction in all ECs while holding Ppull = 0.5 mmHg (66.7 Pa) (mp4 2066 KB)
Deformation of a sinus section under the conditions of Model 2 with the endothelial cell (EC) modulus taken as 10 kPa and LEC = 8 μm. The evolution of the longitudinal strain along the ECs (ε LEC = LE33) is shown first under Ppull = 0 - 1.5 mmHg (0 - 200.0 Pa) with no stress fiber contraction, followed by adding 0 to 30% asymmetric stress fiber contraction in two neighboring ECs while holding Ppull = 1.5 mmHg (200.0 Pa) (mp4 1965 KB)
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Dao, M., MacDonald, I. & Asaro, R.J. Erythrocyte flow through the interendothelial slits of the splenic venous sinus. Biomech Model Mechanobiol 20, 2227–2245 (2021). https://doi.org/10.1007/s10237-021-01503-y
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DOI: https://doi.org/10.1007/s10237-021-01503-y