Role of Band 3 in the Erythrocyte Membrane Structural Changes Under Isotonic and Hypotonic Conditions

An attempt was made to discuss and connect various modeling approaches which have been proposed in the literature in order to shed further light on the erythrocyte membrane relaxation under isotonic and hypotonic conditions. Roles of the main membrane constituents: (1) the actin‐spectrin cortex, (2) the lipid bilayer, and (3) the transmembrane protein band 3 and its course‐consequence relations were considered to estimate the membrane relaxation phenomena. Cell response to loading conditions includes the successive sub‐bioprocesses: (1) erythrocyte local or global deformation, (2) the cortex‐bilayer coupling, and (3) the rearrangements of band 3. The results indicate that the membrane structural changes include: (1) the spectrin flexibility distribution and (2) the rate of its changes influenced by the number of band 3 molecules attached to spectrin filaments, and phosphorylation of the actin‐spectrin junctions. Band 3 rearrangement also influences: (1) the effective bending modulus and (2) the band 3‐bilayer interaction energy and on that base the bilayer bending state. The erythrocyte swelling under hypotonic conditions influences the bilayer integrity which leads to the hemolytic hole formation. The hemolytic hole represents the excited cluster of band 3 molecules

Cell jamming and unjamming in development: physical aspects

Collective cell migration is essential for a wide range of biological processes such as: morphogenesis, wound healing, and cancer spreading. However, it is well known that migrating epithelial collectives frequently undergo jamming, stay trapped some period of time, and then start migration again. Consequently, only a part of epithelial cells actively contributes to the tissue development. In contrast to epithelial cells, migrating mesenchymal collectives successfully avoid the jamming. It has been confirmed that the epithelial unjamming cannot be treated as the epithelial-to-mesenchymal transition. Some other mechanism is responsible for the epithelial jamming/unjamming. Despite extensive research devoted to study the cell jamming/unjamming, we still do not understand the origin of this phenomenon. The origin is connected to physical factors such as: the cell compressive residual stress accumulation and surface characteristics of migrating (unjamming) and resting (jamming) epithelial clusters which depend primarily on the strength of cell-cell adhesion contacts and cell contractility. The main goal of this theoretical consideration is to clarify these cause-consequence relations.Comment: 18 pages, 4 figure

Marangoni effect and cell spreading

Cells are very sensitive to the shear stress (SS). However, undesirable SS is generated during physiological process such as collective cell migration (CCM) and influences the biological processes such as morphogenesis, wound healing and cancer invasion. Despite extensive research devoted to study the SS generation caused by CCM, we still do not fully understand the main cause of SS appearance. An attempt is made here to offer some answers to these questions by considering the rearrangement of cell monolayers. The SS generation represents a consequence of natural and forced convection. While forced convection is dependent on cell speed, the natural convection is induced by the gradient of tissue surface tension. The phenomenon is known as the Marangoni effect. The gradient of tissue surface tension induces directed cell spreading from the regions of lower tissue surface tension to the regions of higher tissue surface tension and leads to the cell sorting. This directional cell migration is described by the Marangoni flux. The phenomenon has been recognized during the rearrangement of (1) epithelial cell monolayers and (2) mixed cell monolayers made by epithelial and mesenchymal cells. The consequence of the Marangoni effect is an intensive spreading of cancer cells through an epithelium. In this work, a review of existing literature about SS generation caused by CCM is given along with the assortment of published experimental findings, to invite experimentalists to test given theoretical considerations in multicellular systems

Role of viscoelasticity in the appearance of low-Reynolds turbulence: Considerations for modelling

Inertial effects caused by perturbations of dynamical equilibrium during the flow of soft matter constitute a hallmark of turbulence. Such perturbations are attributable to an imbalance between energy storage and energy dissipation. During the flow of Newtonian fluids, kinetic energy can be both stored and dissipated, while the flow of viscoelastic soft matter systems, such as polymer fluids, induces the accumulation of both kinetic and elastic energies. The accumulation of elastic energy causes local stiffening of stretched polymer chains, which can destabilise the flow. Migrating multicellular systems are hugely complex and are capable of self-regulating their viscoelasticity and mechanical stress generation, as well as controlling their energy storage and energy dissipation. Since the flow perturbation of viscoelastic systems is caused by the inhomogeneous accumulation of elastic energy, rather than of kinetic energy, turbulence can occur at low Reynolds numbers. This theoretical review is focused on clarifying the role of viscoelasticity in the appearance of low-Reynolds turbulence. Three types of system are considered and compared: (1) high-Reynolds turbulent flow of Newtonian fluids, (2) low and moderate-Reynolds flow of polymer solutions, and (3) migration of epithelial collectives, discussed in terms of two model systems. The models considered involve the fusion of two epithelial aggregates, and the free expansion of epithelial monolayers on a substrate matrix

Viscoelasticity of multicellular surfaces

Various modeling approaches have been applied to describe viscoelasticity of multicellular surfaces. The viscoelasticity is considered within three time regimes: (1) short time regime for milliseconds to seconds time scale which corresponds to sub-cellular level; (2) middle time regime for several tens of seconds to several minutes time scale which corresponds to cellular level; and (3) long time regime for several tens of minutes to several hours time scale which corresponds to supra-celltilar level. Short and middle time regimes have been successfully elaborated in the literature, whereas long time viscoelasticity remains unclear. Long time regime accounts for collective cell migration. Collective cell migration could induce uncorrelated motility which has an impact to energy storage and dissipation during cell surface rearrangement. Uncorrelated motility influences: (1) volume fraction of migrating cells, (2) distribution of migrating cells, (3) shapes of migrating cell groups. These parameters influence mechanical coupling between migrating and resting subpopulations and consequently the constitutive model for long time regime. This modeling consideration indicates that additional experimental work is needed to confirm the feasibility of constitutive models which have been applied in literature for long time regime as: (1) relaxation of stress and strain, (2) storage and loss moduli as the function of time, (3) distribution of migrating cells

Red Blood Cell Deformability Is Expressed by a Set of Interrelated Membrane Proteins

Red blood cell (RBC) deformability, expressing their ability to change their shape, allows them to minimize their resistance to flow and optimize oxygen delivery to the tissues. RBC with reduced deformability may lead to increased vascular resistance, capillary occlusion, and impaired perfusion and oxygen delivery. A reduction in deformability, as occurs during RBC physiological aging and under blood storage, is implicated in the pathophysiology of diverse conditions with circulatory disorders and anemias. The change in RBC deformability is associated with metabolic and structural alterations, mostly uncharacterized. To bridge this gap, we analyzed the membrane protein levels, using mass spectroscopy, of RBC with varying deformability determined by image analysis. In total, 752 membrane proteins were identified. However, deformability was positively correlated with the level of only fourteen proteins, with a highly significant inter-correlation between them. These proteins are involved in membrane rafting and/or the membrane–cytoskeleton linkage. These findings suggest that the reduction of deformability is a programmed (not arbitrary) process of remodeling and shedding of membrane fragments, possibly mirroring the formation of extracellular vesicles. The highly significant inter-correlation between the deformability-expressing proteins infers that the cell deformability can be assessed by determining the level of a few, possibly one, of them

Editorial: Viscoelasticity: From Individual Cell Behavior to Collective Tissue Remodeling

This issue gathers exciting multi-disciplinary work relating viscoelasticity and collective cell remodeling within various biological processes such as morphogenesis, tumorigenesis, and wound healing. Viscoelasticity is influenced by energy transfer and dissipation during cell rearrangement at various time and space scales. Cumulative structural changes at a subcellular level have effects on viscoelasticity at a supracellular level. Established configurations of migrating cells and the rate of their change, which significantly regulate viscoelasticity at a supracellular level, have the impact on the cohesiveness inhomogeneity and various mechanical and biochemical processes at a subcellular level. This Research Topic aims to connect the macroscopic viscoelastic parameters with the individual and collective cell response. Consideration of biochemical, biophysical and bio-mechanical aspects responsible for tissue remodeling, intercalation, and migration were discussed on various multicellular systems under in vivo and in vitro conditions. Thus in this Research Topic we aim to provide a state-of-the-art view about the current knowledge related to viscoelasticity caused by collective cell remodeling and adhesive contractile properties, covering a plethora of phenomena such as: 1) single cell response under stretched monolayers modeled with an improved Vertex model, 2) adhesion percolation within a tissue as an important factor which influences its viscoelasticity, 3) the active turbulence caused by collective cell migration accompanied with the generation of mechanical waves, 4) cell jamming state transitions, and 5) viscoelastic response characterization in liver diseases. Alternative techniques to measure and control cell rearrangement under various experimental conditions are also considered, including atomic force microscopy measurements and various elastography techniques. This Research Topic provides an overview of the current understanding of various: biological, biochemical, biophysical and mechanical aspects of cell remodeling. The inter-relation between cell remodeling and tissue viscoelasticity was discussed by emphasizing the relevant rheological parameters, the way of their measurement under in vivo/ in vitro conditions, and the strategy of multi-scale constitutive modeling

Modeling of the metabolic energy dissipation for restricted tumor growth

Energy dissipation mostly represents unwanted outcome but in the biochemical processes it may alter the biochemical pathways. However, it is rarely considered in the literature although energy dissipation and its alteration due to the changes in cell microenvironment may improve methods for guiding chemical and biochemical processes in the desired directions. Deeper insight into the changes of metabolic activity of tumor cells exposed to osmotic stress or irradiation may offer the possibility of tumor growth reduction. In this work effects of the osmotic stress and irradiation on the thermodynamical affinity of tumor cells and their damping effects on metabolic energy dissipation were investigated and modeled. Although many various models were applied to consider the tumor restrictive growth they have not considered the metabolic energy dissipation. In this work a pseudo rheological model in the form of "the metabolic spring-pot element" is formulated to describe theoretically the metabolic susceptibility of tumor spheroid. This analog model relates the thermodynamical affinity of cell growth with the volume expansion of tumor spheroid under isotropic loading conditions. Spheroid relaxation induces anomalous nature of the metabolic energy dissipation which causes the damping effects on cell growth. The proposed model can be used for determining the metabolic energy "structure" in the context of restrictive cell growth as well as for predicting optimal doses for cancer curing in order to tailor the clinical treatment for each person and each type of cancer