Exploring thermophysical properties of CoCrFeNiCu high entropy alloy via molecular dynamics simulations.

High entropy alloys (HEAs) are alloys composed of five or more primary elements in equal or nearly equal proportions of atoms. In the present study, the thermophysical properties of the CoCrFeNiCu high entropy alloy (HEA) were investigated by a molecular dynamics (MD) method at nanoscale. The effects of the content of individual elements on lattice thermal conductivity k p were revealed, and the results suggested that adjusting the atomic content can be a way to control the lattice thermal conductivity of HEAs. The effects of temperature on k p were investigated quantitively, and a power-law relationship of k p with T -0.419 was suggested, which agrees with previous findings. The effects of temperature and the content of individual elements on volumetric specific heat capacity C v were also studied: as the temperature increases, the C v of all HEAs slightly decreases and then increases. The effects of atomic content on C v varied with the comprising elements. To further understand heat transfer mechanisms in the HEAs, the phonon density of states (PDOS) at different temperatures and varying atomic composition was calculated: Co and Ni elements facilitate the high-frequency vibration of phonons and the Cu environment weakens the heat transfer via low-frequency vibration of photons. As the temperature increases, the phonon mean free path (MFP) in the equiatomic CoCrFeNiCu HEA decreases, which may be attributed to the accelerated momentum of atoms and intensified collisions of phonons. The present research provides theoretical foundations for alloy design and have implications for high-performance alloy smelting.

Effects of Electric Field on Chemical Looping Combustion: A DFT Study of CO Oxidation on CuO (111) Surface.

Chemical looping combustion (CLC) is a promising and novel technology for carbon dioxide (CO2) capture with a relatively low energy consumption and cost. CuO, one of the most attractive oxygen carriers (OCs) for carbon dioxide (CO) oxidation, suffers from sintering and agglomeration during the reduction process. Applying an electric field (EF) may promote the CO oxidation process on the CuO surface, which could mitigate sintering and agglomeration by decreasing operating temperatures with negligible combustion efficiency loss. This study performs density functional theory (DFT) simulations to investigate the effects of EF on the oxidation of CO on the CuO (111) surface. The results indicate that both the orientation and strength of the EF can significantly affect the oxidation characteristics of CO on the CuO (111) surface such as total reaction energy, energy barriers of reactions, CO adsorption, and CO2 desorption. For the first time, this study reveals the role of EF in enhancing CO oxidation through CLC processes via first-principle calculations. Such findings could provide new strategies to improve the performance of CLC processes.

Role of blood flow in endothelial functionality: a review.

Endothelial cells, located on the surface of blood vessel walls, are constantly stimulated by mechanical forces from the blood flow. The mechanical forces, i.e., fluid shear stress, induced by the blood flow play a pivotal role in controlling multiple physiological processes at the endothelium and in regulating various pathways that maintain homeostasis and vascular function. In this review, research looking at different blood fluid patterns and fluid shear stress in the circulation system is summarized, together with the interactions between the blood flow and the endothelial cells. This review also highlights the flow profile as a response to the configurational changes of the endothelial glycocalyx, which is less revisited in previous reviews. The role of endothelial glycocalyx in maintaining endothelium health and the strategies for the restoration of damaged endothelial glycocalyx are discussed from the perspective of the fluid shear stress. This review provides a new perspective regarding our understanding of the role that blood flow plays in regulating endothelial functionality.

Theoretical exploration on the performance of single and dual-atom Cu catalysts on the CO2 electroreduction process: a DFT study.

Carbon dioxide (CO2) electroreduction by metal-nitrogen-doped carbon (MNC) catalysts is a promising and efficient method to mitigate global warming by converting CO2 molecules to value-added chemicals. In this research, we systematically studied the behaviours of single and dual-atom Cu catalysts during the CO2 electroreduction process using density functional theory (DFT) calculations. Two structures, i.e., CuNC-4-pyridine and CuCuNC-4a, were found to be beneficial for C2 chemical generation with relatively high stabilities. Subsequently, we explored the detailed pathways of key products (CO, HCOOH, CH3OH, CH4, C2H6O, C2H4 and C2H6) during CO2 electroreduction on CuNC-4-pyridine and CuCuNC-4a. This research reveals the mechanisms of key product formation during CO2 electroreduction on CuNC-4-pyridine and CuCuNC-4a, which would provide important insights to guide the design of MNC catalysts with low limiting potentials and high product selectivity.

Molecular dynamics simulation: A new way to understand the functionality of the endothelial glycocalyx.

Endothelial glycocalyx (EG) is a carbohydrate-rich layer which lines the lumen side of blood vessel walls. The EG layer is directly exposed to blood flow. The unique physiological location and its strongly coupled interaction with blood flow allow the EG layer to modulate microvascular mass transport and to sense and transmit mechanical signals from the passing blood. Molecular dynamics (MD) simulation is a computational method which focuses on atomic/molecular behavior at the microscale. The last two decades have witnessed a substantial increase in number and a broadening in scope regarding applications of MD in a wide spectrum of areas, including EG-related research. In this mini-review, MD works which solve EG-related problems and provide new insights into the functionality of EG are considered. Challenges of the MD method in EG research are articulated, and the future of MD in solving EG-related problems is also evaluated.

Biomechanical properties of endothelial glycocalyx: An imperfect pendulum.

Endothelial glycocalyx plays a crucial role in hemodynamics in health and disease, yet studying it is met by multiple technical hindrances. We attempted to outline our views on some biomechanical properties of endothelial glycocalyx, which are potentially amenable to mathematical modeling. We start with the null-hypothesis ascribing to glycocalyx the properties of a pendulum and reject this hypothesis on the grounds of multiple obstacles for pendulum behavior, such as rich decoration with flexible negatively charged side-chains, variable length and density, fluid fixation to the plasma membrane. We next analyze the current views on membrane attachments to the cortical actin web, its pulsatile contraction-relaxation cycles which rebound to the changes in tension of the plasma membrane. Based on this, we consider the outside-in signaling, the basis for mechanotransduction, and the dampening action of the inside-out signaling. The aperiodic oscillatory motions of glycocalyx and cortical actin web underlie our prediction of two functional pacemakers. We next advance an idea that the glycocalyx, plasma membrane, and cortical actin web represent a structure-functional unit and propose the concept of tensegrity model. Finally, we present our recent data suggesting that erythrocytes are gliding or hovering and rotating over the surface of intact glycocalyx, whereas the rotational and hovering components of their passage along the capillaries are lost when glycocalyx of either is degraded. These insights into the mechanics of endothelial glycocalyx motions may be of value in crosspollination between biomechanics, physiology, and pathophysiology for deeper appreciation of its rich untapped resources in health and pharmacotherapy in disease.

Understanding the Role of Endothelial Glycocalyx in Mechanotransduction via Computational Simulation: A Mini Review.

Endothelial glycocalyx (EG) is a forest-like structure, covering the lumen side of blood vessel walls. EG is exposed to the mechanical forces of blood flow, mainly shear, and closely associated with vascular regulation, health, diseases, and therapies. One hallmark function of the EG is mechanotransduction, which means the EG senses the mechanical signals from the blood flow and then transmits the signals into the cells. Using numerical modelling methods or in silico experiments to investigate EG-related topics has gained increasing momentum in recent years, thanks to tremendous progress in supercomputing. Numerical modelling and simulation allows certain very specific or even extreme conditions to be fulfilled, which provides new insights and complements experimental observations. This mini review examines the application of numerical methods in EG-related studies, focusing on how computer simulation contributes to the understanding of EG as a mechanotransducer. The numerical methods covered in this review include macroscopic (i.e., continuum-based), mesoscopic [e.g., lattice Boltzmann method (LBM) and dissipative particle dynamics (DPD)] and microscopic [e.g., molecular dynamics (MD) and Monte Carlo (MC) methods]. Accounting for the emerging trends in artificial intelligence and the advent of exascale computing, the future of numerical simulation for EG-related problems is also contemplated.

Cross talk between endothelial and red blood cell glycocalyces via near-field flow.

Vascular endothelial cells and circulating red blood cell (RBC) surfaces are both covered by a layer of bushy glycocalyx. The interplay between these glycocalyx layers is hardly measurable and insufficiently understood. This study aims to investigate and qualify the possible interactions between the glycocalyces of RBCs and endothelial cells using mathematical modeling and numerical simulation. Dissipative particle dynamics (DPD) simulations are conducted to investigate the response of the endothelial glycocalyx (EG) to varying ambient conditions. A two-compartment model including EG and flow and a three-compartment model comprising EG, RBC glycocalyx, and flow are established. The two-compartment analysis shows that a relatively fast flow is associated with a predominantly bending motion of the EG, whereas oscillatory motions are predominant in a relatively slow flow. Results show that circulating RBCs cause the contactless deformation of EG. Its deformation is dependent on the chain layout, chain length, bending stiffness, RBC-to-EG distance, and RBC velocities. Specifically, shorter EG chains or RBC-to-EG distance leads to greater relative deflections of EG. Deformation of EG is enhanced when the EG chains are rarefied or RBCs move faster. The bending stiffness maintains stretching conformation of EG. Moreover, a compact EG chain layout and shedding EG chains disturb the neighboring flow field, causing disordered flow velocity distributions. In contrast, the movement of EG chains on RBC surfaces exerts a marginal driving force on RBCs. The DPD method is used for the first time, to our knowledge, in the three-compartment system to explore the cross talk between EG and RBC glycocalyx. This study suggests that RBCs drive the EG deformation via the near-field flow, whereas marginal propulsion of RBCs by the EG is observed. These new, to our knowledge, findings provide a new angle to understand the roles of glycocalyx in mechanotransduction and microvascular permeability and their perturbations under idealized pathophysiologic conditions associated with EG degradation.

Sodium ion transport across the endothelial glycocalyx layer under electric field conditions: A molecular dynamics study.

In the present research, the sodium ion transport across the endothelial glycocalyx layer (EGL) under an imposed electric field is investigated, for the first time, using a series of molecular dynamics simulations. The electric field is perpendicularly imposed on the EGL with varying strengths. The sodium ion molarity difference between the inner and outer layers of EGL, Δc, is used to quantify the sodium transport in the presence of the negatively charged glycocalyx sugar chains. Results suggest that a weak electric field increases Δc, regardless of whether the electric field is imposed perpendicularly inward or outward. By contrast, a strong electric field drives sodium ions to travel in the same orientation as the electric field. Scrutiny of the charge distribution of the glycocalyx sugar chains suggests that the electric field modifies the spatial layouts of glycocalyx atoms as it drives the transport of sodium ions. The modification in glycocalyx layouts further changes the inter-molecular interactions between glycocalyx sugar chains and sodium ions, thereby limiting the electric field control of ion transport. The sodium ions, in turn, alter the apparent bending stiffness of glycocalyx. Moreover, the negative charges of the glycocalyx sugar chains play an important role in maintaining structural stability of endothelial glycocalyx. Based on the findings, a hypothesis is proposed regarding the existence of a strength threshold of the electric field in controlling charged particles in the endothelium, which offers an alternative explanation for contrasting results in previous experimental observations.

Membrane Deformation of Endothelial Surface Layer Interspersed with Syndecan-4: A Molecular Dynamics Study.

The lipid membrane of endothelial cells plays a pivotal role in maintaining normal circulatory system functions. To investigate the response of the endothelial cell membrane to changes in vascular conditions, an atomistic model of the lipid membrane interspersed with Syndecan-4 core protein was established based on experimental observations and a series of molecular dynamics simulations were undertaken. The results show that flow results in continuous deformation of the lipid membrane, and the degree of membrane deformation is not in monotonic relationship with the environmental changes (either the changes in blood velocity or the alteration of the core protein configuration). An explanation for such non-monotonic relationship is provided, which agrees with previous experimental results. The elevation of the lipid membrane surface around the core protein of the endothelial glycocalyx was also observed, which can be mainly attributed to the Coulombic interactions between the biomolecules therein. The present study demonstrates that the blood flow can deform the lipid membrane directly via the interactions between water molecules and lipid membrane atoms thereby affecting mechanosensing; it also presents an additional force transmission pathway from the flow to the lipid membrane via the glycocalyx core protein, which complements previous mechanotransduction hypothesis.

Principal mode of Syndecan-4 mechanotransduction for the endothelial glycocalyx is a scissor-like dimer motion.

AIM: Endothelial glycocalyx (EG) plays a pivotal role in a plethora of diseases, like cardiovascular and renal diseases. One hallmark function of the EG as a mechanotransducer which transmits mechanical signals into cytoplasm has been documented for decades. However, the basic question - how the glycocalyx transmits the flow shear stress- is unanswered so far. Our aim is to shed light on the fundamental mode of signal transmission from flow to the endothelial cytoskeleton. METHODS: We conduct a series of large-scale molecular dynamics computational experiments to investigate the dynamics of glycocalyx under varying conditions (changing blood flow velocities and shedding of glycocalyx sugar chains). RESULTS: We have identified that the main pathway of signal transmission in this system manifests as a scissors-like motion of the Syndecan-4 core protein. Results have suggested that the force transmitted into the cytoskeleton with an order of 10 ~ 100 pN, and the main function of sugar chains of a glycocalyx element is to protect the core proteins from severe conformational changes thereby maintaining the functionality of the EG. CONCLUSION: This research provides a reconciling explanation for a longstanding debate about the force transmission threshold based on our findings. A new explanation has also been provided to relate the role of the EG as a mechanotransducer to its function as a microvascular barrier: the EG regulates the mechanotransduction by altering the median value and variation range of the scissor angle, and the EG governs the microvascular barrier via controlling the scissor angle which will affect the intercellular cleft.

Microvascular ion transport through endothelial glycocalyx layer: new mechanism and improved Starling principle.

Ion transport through the endothelial glycocalyx layer is closely associated with many vascular diseases. Clarification of ion behaviors around the endothelial glycocalyx layer under varying circumstances will benefit pathologies related to cardiovascular and renal diseases. In this research, a series of large-scale molecular dynamics simulations are conducted to study the response of ion transport to the changing blood flow velocity and the shedding of endothelial glycocalyx sugar chains. Results indicate that blood flow promotes the outward Na+ transport from the near-membrane region to the lumen via the endothelial glycocalyx layer. Scrutiny of sugar-chain dynamics and their interactions with Na+ suggests that corner conformation of endothelial glycocalyx sugar chains confines the movement of the Na+, whereas stretching conformation facilitates the motion of Na+ ions. The flow impact on ion transport of Na+ is nonlinear. Based on the findings, the Starling principle and its revised version, which are prevailingly used to predict the ion transport of the endothelial glycocalyx layer, are further improved. An estimation based on the further revised Starling principle indicates that physiological flow changes the osmotic part of transendothelial water flux by 8% compared with the stationary situation. NEW & NOTEWORTHY The biophysical roles of negatively charged oligosaccharides of the endothelial glycocalyx have gained increasing attention due to their importance in regulating microvascular fluid exchange. The Starling principle and its revisions are at the heart of the understanding of fluid homeostasis in the periphery. Here, the blood flow changes the conformations of glycocalyx sugar chains, thereby influencing availability of Na+ for transport. Based on the findings, the Starling principle and its revision are further improved.

Understanding endothelial glycocalyx function under flow shear stress from a molecular perspective.

BACKGROUND: The endothelial glycocalyx plays a pivotal role in regulating blood flow, filtering blood components, sensing and transducing mechanical signals. These functions are intimately related to its dynamics at the molecular level. OBJECTIVE: The objective of this research is to establish the relationship between the functions of the endothelial glycocalyx and its dynamics at the molecular level. METHODS: To establish such a relationship, large-scale molecular dynamics simulations were undertaken to mimic the dynamics of the glycocalyx and its components in the presence of flow shear stresses. RESULTS: First, motions of the glycocalyx core protein and the pertinent subdomains were scrutinised. Three-directional movements of the glycocalyx core protein were observed, although the flow was imposed only in the x direction. Such an observation contributes to understanding the glycocalyx redistribution as reported in experiments. Unsynchronised motion of the core protein subdomains was also spotted, which provides an alternative explanation of macroscopic phenomena. Moreover, the dynamics, root-mean-square-deviations and conformational changes of the sugar chains were investigated. Based on the findings, an alternative force transmission pathway, the role of sugar chains, and potential influence on signalling transduction pathways were proposed and discussed. CONCLUSIONS: This study relates the functions of the glycocalyx with its microscopic dynamics, which fills a knowledge gap about the links between different scales.

Reducing Salt Intake and Exercising Regularly: Implications From Molecular Dynamics Simulations of Endothelial Glycocalyx.

It is widely accepted that salt intake reduction and regular exercise is a healthy lifestyle, which can prevent cardiovascular diseases (CVD). Meanwhile, there is evidence that the endothelial glycocalyx layer (EGL) is related to CVD. However, how such a healthy lifestyle helps to prevent CVD via the function of the EGL has not been scientifically established. In this research, a series of large-scale molecular dynamics simulations have been conducted to study ion transport inside the EGL under varying flow velocities. Results show that a fast blood flow velocity favors the Na+ transport out of the EGL, which can explain the increase in the thickness of an exclusion layer between red blood cells and the EGL under fast blood flow situations, as witnessed in some previous experiments. Based on findings from this fundamental research, a theory is proposed, which can answer the open-ended question "Why do we need to reduce salt intake and exercise regularly". The findings may also have implications for other therapies to combat cardiovascular diseases.

Regimes of Flow over Complex Structures of Endothelial Glycocalyx: A Molecular Dynamics Simulation Study.

Flow patterns on surfaces grafted with complex structures play a pivotal role in many engineering and biomedical applications. In this research, large-scale molecular dynamics (MD) simulations are conducted to study the flow over complex surface structures of an endothelial glycocalyx layer. A detailed structure of glycocalyx has been adopted and the flow/glycocalyx system comprises about 5,800,000 atoms. Four cases involving varying external forces and modified glycocalyx configurations are constructed to reveal intricate fluid behaviour. Flow profiles including temporal evolutions and spatial distributions of velocity are illustrated. Moreover, streamline length and vorticity distributions under the four scenarios are compared and discussed to elucidate the effects of external forces and glycocalyx configurations on flow patterns. Results show that sugar chain configurations affect streamline length distributions but their impact on vorticity distributions is statistically insignificant, whilst the influence of the external forces on both streamline length and vorticity distributions are trivial. Finally, a regime diagram for flow over complex surface structures is proposed to categorise flow patterns.

Large-scale molecular dynamics simulation of coupled dynamics of flow and glycocalyx: towards understanding atomic events on an endothelial cell surface.

The glycocalyx has a prominent role in orchestrating multiple biological processes occurring at the plasma membrane. In this paper, an all-atom flow/glycocalyx system is constructed with the bulk flow velocity in the physiologically relevant ranges for the first time. The system is simulated by molecular dynamics using 5.8 million atoms. Flow dynamics and statistics in the presence of the glycocalyx are presented and discussed. Complex dynamic behaviours of the glycocalyx, particularly the sugar chains, are observed in response to blood flow. In turn, the motion of the glycocalyx, including swing and swirling, disturbs the flow by altering the velocity profiles and modifying the vorticity distributions. As a result, the initially one-dimensional forcing is spread to all directions in the region near the endothelial cell surface. Furthermore, the coupled dynamics exist not only between the flow and the glycocalyx but also within the glycocalyx molecular constituents. Shear stress distributions between one-dimer and three-dimer cases are also conducted. Finally, potential force transmission pathways are discussed based on the dynamics of the glycocalyx constituents, which provides new insight into the mechanism of mechanotransduction of the glycocalyx. These findings have relevance in the pathologies of glycocalyx-related diseases, for example in renal or cardiovascular conditions.