scholarly journals Balance of microtubule stiffness and cortical tension determines the size of blood cells with marginal band across species

2016 ◽  
Author(s):  
Serge Dmitrieff ◽  
Adolfo Alsina ◽  
Aastha Mathur ◽  
François Nedéléc

The fast blood stream of animals is associated with large shear stresses. Consequently, blood cells have evolved a special morphology and a specific internal architecture allowing them to maintain their integrity over several weeks. For instance, non-mammalian red blood cells, mammalian erythroblasts and platelets have a peripheral ring of microtubules, called the marginal band, that flattens the overall cell morphology by pushing on the cell cortex. In this article, we model how the shape of these cells stems from the balance between marginal band elasticity and cortical tension. We predict that the diameter of the cell scales with the total microtubule polymer, and verify the predicted law across a wide range of species. Our analysis also shows that the combination of the marginal band rigidity and cortical tension increases the ability of the cell to withstand forces without deformation. Finally, we model the marginal band coiling that occurs during the disc-to-sphere transition observed for instance at the onset of blood platelet activation. We show that when cortical tension increases faster than crosslinkers can unbind, the marginal band will coil, whereas if the tension increases slower, the marginal band may shorten as microtubules slide relative to each other.Significance StatementMany blood cells have a discoidal shape, which is essential for them to function properly within the organism. For some cells, such as blood platelets, this shape is due to the interplay between the elasticity of the marginal band, which is a closed ring of stiff filaments called microtubules, and the tension of the cell cortex, a polymer scaffold associated with the plasma membrane. Dmitrieff et al. examined how cell size is determined by the mechanical balance between these two components. Remarkably, the theory is confirmed over nearly three orders of magnitudes, by data collected from 25 species. The theory also shows how the composite structure is adapted to resist transient mechanical challenges, as encountered in the blood stream.

2017 ◽  
Vol 114 (17) ◽  
pp. 4418-4423 ◽  
Author(s):  
Serge Dmitrieff ◽  
Adolfo Alsina ◽  
Aastha Mathur ◽  
François J. Nédélec

The fast bloodstream of animals is associated with large shear stresses. To withstand these conditions, blood cells have evolved a special morphology and a specific internal architecture to maintain their integrity over several weeks. For instance, nonmammalian red blood cells, mammalian erythroblasts, and platelets have a peripheral ring of microtubules, called the marginal band, that flattens the overall cell morphology by pushing on the cell cortex. In this work, we model how the shape of these cells stems from the balance between marginal band rigidity and cortical tension. We predict that the diameter of the cell scales with the total microtubule polymer and verify the predicted law across a wide range of species. Our analysis also shows that the combination of the marginal band rigidity and cortical tension increases the ability of the cell to withstand forces without deformation. Finally, we model the marginal band coiling that occurs during the disk-to-sphere transition observed, for instance, at the onset of blood platelet activation. We show that when cortical tension increases faster than cross-linkers can unbind, the marginal band will coil, whereas if the tension increases more slowly, the marginal band may shorten as microtubules slide relative to each other.


2011 ◽  
Vol 105 (S 06) ◽  
pp. S13-S33 ◽  
Author(s):  
Alan Nurden

SummaryBlood platelets have long been recognised to bring about primary haemostasis with deficiencies in platelet production and function manifesting in bleeding while upregulated function favourises arterial thrombosis. Yet increasing evidence indicates that platelets fulfil a much wider role in health and disease. First, they store and release a wide range of biologically active substances including the panoply of growth factors, chemokines and cytokines released from α-granules. Membrane budding gives rise to microparticles (MPs), another active participant within the blood stream. Platelets are essential for the innate immune response and combat infection (viruses, bacteria, micro-organisms). They help maintain and modulate inflammation and are a major source of pro-inflammatory molecules (e.g. P-selectin, tissue factor, CD40L, metalloproteinases). As well as promoting coagulation, they are active in fibrinolysis; wound healing, angiogenesis and bone formation as well as in maternal tissue and foetal vascular remodelling. Activated platelets and MPs intervene in the propagation of major diseases. They are major players in atherosclerosis and related diseases, pathologies of the central nervous system (Alzheimers disease, multiple sclerosis), cancer and tumour growth. They participate in other tissue-related acquired pathologies such as skin diseases and allergy, rheumatoid arthritis, liver disease; while, paradoxically, autologous platelet-rich plasma and platelet releasate are being used as an aid to promote tissue repair and cellular growth. The above mentioned roles of platelets are now discussed.


2017 ◽  
Vol 112 (3) ◽  
pp. 126a
Author(s):  
Serge A. Dmitrieff ◽  
Adolfo Alsina ◽  
Mathur Aastha ◽  
Nédélec François

Author(s):  
O. Behnke ◽  
J. Tranum-Jensen

Within the last decade the mammalian blood platelet has enjoyed a rapidly increasing popularity as a research object. It is widely appreciated that platelets are multifunctional, and that they play a role in a variety of physiological and pathological processes besides their main function: the formation and consolidation of a haemostatic plug (for a recent monograph, and for references, see Gordon, 1976). The platelet is an anucleate piece of cytoplasm, pinched off from megakaryocytes (MK) in the bone marrow or in the circulation (Tinggaard Petersen, 1974). Vital microscopy has shown that in the circulation the platelet is disc-shaped, that it normally does not stick to endothelium or to other blood cells, and that it is the least deformable cell in blood - the latter observation does suggest the presence of a rigid skeleton in the platelet cytoplasm.


1937 ◽  
Vol 83 (343) ◽  
pp. 175-189
Author(s):  
D. K. Bruce

On looking through the literature relating to the blood-picture in various types of mental disorders, one finds that most workers have confined themselves to the red and white cells only. Relatively little attention has been given to the study of the third element of the blood, namely, the blood-platelet. It is now almost universally accepted that the blood-platelet is a constant element in normal blood, and it has been shown both clinically and experimentally that in health and in disease the platelets fluctuate independently of the red and white cells. In toxic conditions there is agreement that the platelets fall in the acute stages, and that during convalescence their numbers tend to increase, after which there is a gradual fall to the normal limits. This constant behaviour of the platelets has been observed in certain acute infectious diseases, in pneumonia and in typhoid fever. Certain writers think that the platelets have an important function in eliminating foreign bodies from the blood, or play some part in establishing a state of immunity to infection. This part played by the platelets in the sterility of the blood-stream suggests an explanation for the reduced numbers in acute infections. Diminution would be due to the using-up of the platelets in removing and destroying the infective agents or their products. The present work gives the results of an attempt to show that this same relation between the platelets and toxins also exists during certain phases of mental disorder and, in these particular cases, a toxin from a focus of infection can be assumed to be the causative agent in producing the psychosis.


Blood ◽  
1957 ◽  
Vol 12 (8) ◽  
pp. 733-745 ◽  
Author(s):  
RICHARD WAGNER ◽  
NORMA MEYERRIECKS ◽  
CARROLL Z. BERMAN

Abstract 1) Alkaline phosphatase activity of leukocytes is enhanced by radiation with 50,000 r. This disturbance accentuates the inherent aging process of white blood cells and may be explained by changes in the cell envelope. 2) X-radiation diminishes the endogenous oxygen uptake of leukocyte-platelet suspensions by approximately 20 per cent. This response to radiation is demonstrable at exposures of as little as 5,000 r. The decreasing effect is diminished when substrates such as sodium succinate or α-glycerophosphate are added, within a wide range of their concentration. With increasing substrate concentration the decrease due to radiation approaches that of the endogenous respiration and even exceeds it in some of the experiments. 3) In pure blood platelets a similar decreasing x-radiation effect occurs for endogenous respiration as well as succinic dehydrogenase activity; α-glycerophosphate dehydrogenase activity, on the other hand, is enhanced. 4) The oxygen uptake in leukocyte-platelet suspensions due only to leukocytes can be calculated. While the percentage radiation decrease of pure leukocytes is unchanged for endogenous and succinate activity, the decrease for α-glycerophosphate as substrate reaches considerably higher levels (68 per cent compared with 8.2 per cent in leukocyte-platelet suspensions). Thus α-glycerophosphate dehydrogenase activity seems to be most sensitive to x-radiation. It was shown in one of our previous studies that α-glycerophosphate dehydrogenase is one of the most important respiratory enzymes in leukocytes. 5) The glycolytic system in leukocytes remains intact following exposure to radiation with 50,000 r.


1964 ◽  
Vol 12 (01) ◽  
pp. 179-200 ◽  
Author(s):  
Torstein Hovig

SummaryThe effect of calcium and magnesium on the aggregation of rabbit blood platelets in vitro was studied, with the following results:1. Platelet aggregation induced by ADP or collagen could be prevented by EGTA or EDTA. The aggregating effect was restored by recalcification. The effect was also restored by addition of magnesium in EDTA-PRP, but not in EGTA-PRP unless a surplus of calcium was present.2. Calcium remained in concentrations of the order of 0.15–0.25 mM after dialysis or cation exchange of plasma. Aggregation of washed platelets resuspended in such plasma could not be produced with ADP or collagen, unless the calcium concentration was increased or that magnesium was added.3. The adhesiveness of blood platelets to collagen was reduced in EGTA-PRP and EDTA-PRP. Release of ADP from platelets influenced by collagen could not be demonstrated either in EGTA-PRP (presence of magnesium) or in EDTA-PRP.4. It is concluded that calcium is a necessary factor both for the reaction leading to release of ADP and for the the aggregation produced by ADP.5. Thrombin induced aggregation of washed platelets suspended in tris-buffered saline in the presence of calcium. No effect of magnesium could be observed unless small quantities of calcium were present.


2021 ◽  
pp. 1-10
Author(s):  
Rui Zhong ◽  
Dingding Han ◽  
Xiaodong Wu ◽  
Hong Wang ◽  
Wanjing Li ◽  
...  

Background: The hypoxic environment stimulates the human body to increase the levels of hemoglobin (HGB) and hematocrit and the number of red blood cells. Such enhancements have individual differences, leading to a wide range of HGB in Tibetans’ whole blood (WB). Study Design: WB of male Tibetans was divided into 3 groups according to different HGB (i.e., A: >120 but ≤185 g/L, B: >185 but ≤210 g/L, and C: >210 g/L). Suspended red blood cells (SRBC) processed by collected WB and stored in standard conditions were examined aseptically on days 1, 14, 21, and 35 after storage. The routine biochemical indexes, deformability, cell morphology, and membrane proteins were tested. Results: Mean corpuscular volume, adenosine triphosphate, pH, and deformability were not different in group A vs. those in storage (p > 0.05). The increased rate of irreversible morphology of red blood cells was different among the 3 groups, but there was no difference in the percentage of red blood cells with an irreversible morphology after 35 days of storage. Group C performed better in terms of osmotic fragility and showed a lower rigid index than group A. Furthermore, SDS-PAGE revealed similar cross-linking degrees of cell membrane protein but the band 3 protein of group C seemed to experience weaker clustering than that of group A as detected by Western Blot analysis after 35 days of storage. Conclusions: There was no difference in deformability or morphological changes in the 3 groups over the 35 days of storage. High HGB levels of plateau SRBC did not accelerate the RBC change from a biconcave disc into a spherical shape and it did not cause a reduction in deformability during 35 days of preservation in bank conditions.


Author(s):  
Wenwen Shen ◽  
Terry Griffiths ◽  
Mengmeng Xu ◽  
Jeremy Leggoe

For well over a decade it has been widely recognised that existing models and tools for subsea pipeline stability design fail to account for the fact that seabed soils tend to become mobile well before the onset of pipeline instability. Despite ample evidence obtained from both laboratory and field observations that sediment mobility has a key role to play in understanding pipeline/soil interaction, no models have been presented previously which account for the tripartite interaction between the fluid and the pipe, the fluid and the soil, and the pipe and the soil. There are numerous well developed and widely used theories available to model pipe-fluid and pipe-soil interactions. A challenge lies in the way to develop a satisfactory fluid-soil interaction algorithm that has the potential for broad implementation under both ambient and extreme sea conditions due to the complexity of flow in the vicinity of a seabed pipeline or cable. A widely used relationship by Shields [1] links the bedload and suspended sediment transport to the seabed shear stresses. This paper presents details of computational fluid dynamics (CFD) research which has been undertaken to investigate the variation of seabed shear stresses around subsea pipelines as a parametric function of pipeline spanning/embedment, trench configuration and wave/current properties using the commercial RANS-based software ANSYS Fluent. The modelling work has been undertaken for a wide range of seabed geometries, including cases in 3D to evaluate the effects of finite span length, span depth and flow attack angle on shear stresses. These seabed shear stresses have been analysed and used as the basis for predicting sediment transport within the Pipe-Soil-Fluid (PSF) Interaction Model [2] in determining the suspended sediment concentration and the advection velocity in the vicinity of pipelines. The model has significant potential to be of use to operators who struggle with conventional stabilisation techniques for the pipelines, such as those which cross Australia’s North West Shelf, where shallow water depths, highly variable calcareous soils and extreme metocean conditions driven by frequent tropical cyclones result in the requirement for expensive and logistically challenging secondary stabilisation measures.


2006 ◽  
Vol 17 (7) ◽  
pp. 3009-3020 ◽  
Author(s):  
Johan-Owen De Craene ◽  
Jeff Coleman ◽  
Paula Estrada de Martin ◽  
Marc Pypaert ◽  
Scott Anderson ◽  
...  

The endoplasmic reticulum (ER) contains both cisternal and reticular elements in one contiguous structure. We identified rtn1Δ in a systematic screen for yeast mutants with altered ER morphology. The ER in rtn1Δ cells is predominantly cisternal rather than reticular, yet the net surface area of ER is not significantly changed. Rtn1-green fluorescent protein (GFP) associates with the reticular ER at the cell cortex and with the tubules that connect the cortical ER to the nuclear envelope, but not with the nuclear envelope itself. Rtn1p overexpression also results in an altered ER structure. Rtn proteins are found on the ER in a wide range of eukaryotes and are defined by two membrane-spanning domains flanking a conserved hydrophilic loop. Our results suggest that Rtn proteins may direct the formation of reticulated ER. We independently identified Rtn1p in a proteomic screen for proteins associated with the exocyst vesicle tethering complex. The conserved hydophilic loop of Rtn1p binds to the exocyst subunit Sec6p. Overexpression of this loop results in a modest accumulation of secretory vesicles, suggesting impaired exocyst function. The interaction of Rtn1p with the exocyst at the bud tip may trigger the formation of a cortical ER network in yeast buds.


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