Erythrocyte: A systems model of the control of aggregation and deformability

Bazanovas, Antonina N.; A, Evstifeev; Khaiboullina, Svetlana F.; Sadreev, Ildar I.; Skorinkin, A. I.; Kotov, Nikolay V.

doi:10.1016/j.biosystems.2015.03.003

Cited by 9 publications

(7 citation statements)

References 46 publications

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“…It has been speculated that phosphorylation of band 3 is the main molecular determinant controlling deformability and aggregation (Bazanovas et al, 2015). Band 3 plays a key role in many aspects of the RBC aging process, which is associated with alterations in deformability and aggregation (Bosman et al, 2010).…”

Section: Deformability and Aggregationmentioning

confidence: 99%

The Relationship Between Aggregation and Deformability of Red Blood Cells in Health and Disease

et al. 2020

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The molecular organization of the membrane of the red blood cell controls cell morphology and function and is thereby a main determinant of red blood cell homeostasis in the circulation. The role of membrane organization is prominently reflected in red blood cell deformation and aggregation. However, there is little knowledge on whether they are controlled by the same membrane property and if so, to what extent. To address the potential interdependence of these two parameters, we measured deformation and aggregation in a variety of physiological as well as pathological conditions. As a first step, we correlated a number of deformability and aggregation parameters in red blood cells from healthy donors, which we obtained in the course of our studies on red blood cell homeostasis in health and disease. This analysis yielded some statistically significant correlations. Also, we found that most of these correlations were absent in misshapen red blood cells that have an inborn defect in the interaction between the membrane and the cytoskeleton. The observations suggest that deformability and aggregation share at least one common, membrane-related molecular mechanism. Together with data obtained after treatment with various agents known to affect membrane organization in vitro, our findings suggest that a phosphorylationcontrolled interaction between the cytoskeleton and the integral membrane protein band 3 is part of the membrane-centered mechanism that plays a role in deformability as well as aggregation.

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Section: Deformability and Aggregationmentioning

confidence: 99%

The Relationship Between Aggregation and Deformability of Red Blood Cells in Health and Disease

et al. 2020

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“…2c ) may result in the switch-like response and ultrasensitivity of the protein activation [ 50 ]. For instance, the steepness of CaM activation defines the threshold properties for the switching of erythrocyte aggregation and deformability from one steady-state to another [ 51 ].…”

Section: The Model For Abundant Ligand Concentrationmentioning

confidence: 99%

Kinetic regulation of multi-ligand binding proteins

et al. 2016

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BackgroundSecond messengers, such as calcium, regulate the activity of multisite binding proteins in a concentration-dependent manner. For example, calcium binding has been shown to induce conformational transitions in the calcium-dependent protein calmodulin, under steady state conditions. However, intracellular concentrations of these second messengers are often subject to rapid change. The mechanisms underlying dynamic ligand-dependent regulation of multisite proteins require further elucidation.ResultsIn this study, a computational analysis of multisite protein kinetics in response to rapid changes in ligand concentrations is presented. Two major physiological scenarios are investigated: i) Ligand concentration is abundant and the ligand-multisite protein binding does not affect free ligand concentration, ii) Ligand concentration is of the same order of magnitude as the interacting multisite protein concentration and does not change. Therefore, buffering effects significantly influence the amounts of free ligands. For each of these scenarios the influence of the number of binding sites, the temporal effects on intermediate apo- and fully saturated conformations and the multisite regulatory effects on target proteins are investigated.ConclusionsThe developed models allow for a novel and accurate interpretation of concentration and pressure jump-dependent kinetic experiments. The presented model makes predictions for the temporal distribution of multisite protein conformations in complex with variable numbers of ligands. Furthermore, it derives the characteristic time and the dynamics for the kinetic responses elicited by a ligand concentration change as a function of ligand concentration and the number of ligand binding sites. Effector proteins regulated by multisite ligand binding are shown to depend on ligand concentration in a highly nonlinear fashion.

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“…The late 1980s saw the development of the first whole-cell model of the human RBC [ 2 – 5 ]. Since then, other models of the RBC have focused on various aspects of its physiology, from metabolism [ 6 ] to its structural properties [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Systems biology as an emerging paradigm in transfusion medicine

2018

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Blood transfusions are an important part of modern medicine, delivering approximately 85 million blood units to patients annually. Recently, the field of transfusion medicine has started to benefit from the “omic” data revolution and corresponding systems biology analytics. The red blood cell is the simplest human cell, making it an accessible starting point for the application of systems biology approaches.In this review, we discuss how the use of systems biology has led to significant contributions in transfusion medicine, including the identification of three distinct metabolic states that define the baseline decay process of red blood cells during storage. We then describe how a series of perturbations to the standard storage conditions characterized the underlying metabolic phenotypes. Finally, we show how the analysis of high-dimensional data led to the identification of predictive biomarkers.The transfusion medicine community is in the early stages of a paradigm shift, moving away from the measurement of a handful of chosen variables to embracing systems biology and a cell-scale point of view.

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Erythrocyte: A systems model of the control of aggregation and deformability

Cited by 9 publications

References 46 publications

The Relationship Between Aggregation and Deformability of Red Blood Cells in Health and Disease

The Relationship Between Aggregation and Deformability of Red Blood Cells in Health and Disease

Kinetic regulation of multi-ligand binding proteins

Systems biology as an emerging paradigm in transfusion medicine

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