Modelowanie komputerowe i analityczne bioinspirowanego, standardowego układu fizyki powierzchni, w zakresie tarcia i smarowania, na wybranym przykładzie

This thesis presents a description of friction and lubrication mechanisms when applied to natural system of articular cartilage. The presented model of facilitated lubrication of articular cartilage explains a multiscale phenomenon during application of an external quasi-normal load to the surfaces. The model is applied to explain degeneration of articular cartilage surface as well as synovial fluid in terms of its composition. Molecular dynamics simulations as well as analytical description are employed to describe these phenomena. Presented work is divided into 7 chapters. First chapter describes the theory behind friction and lubrication. The chapter consists of 5 subsections essential for understanding all occurrences in the system. First one introduces friction and lubrication phenomenon. The basics of Soft Matter Physics as well as physiology of articular cartilage are presented in terms of their connection to friction/lubrication mechanism. Finally, the key factors of hydration repulsion and Grotthuss mechanism are discussed. Second chapter presents the theory of molecular dynamics simulation and its several varieties: full-atom, coarse grained and steered molecular dynamics. Third section depicts a facilitated lubrication mechanism. The model is delivered by applying dispersive kinetics as a description of PLs concentration fields. Then by modification of model variables one can discuss a physical explanation. Finally, MNET dynamics is used to describe dynamics of proton channels as interplay between overcrowding of protons and confinement of a channel. Fourth part presents on hyaluronic acid and phospholipids interactions. The literature study provides a first step towards understanding processes occurring in normal and abnormal synovial fluid. Results of microelectrophoresis on HA/PL complexes are presented in terms of cross-linking mechanism as well as proton transport. Finally, molecular dynamics simulations of HA:PL complexes are presented for different pHs and PLs concentrations. The results are rationalized in terms of Rouse model. Fifth chapter presents steered molecular dynamics study on micelles’ interactions and their impact on overall process. Sixth part presents recapitulation of all works published for this thesis and a connection between them. The last chapter summarizes and addresses a future application of presented studies

Formation of Protein Networks between Mucins: Molecular Dynamics Study Based on the Interaction Energy of the System

Molecular dynamics simulations have been performed for a model aqueous solution of mucin. As mucin is a central part of lubricin, a key component of synovial fluid, we investigate its ability to form cross-linked networks. Such network formation could be of major importance for the viscoelastic properties of the soft-matter system and crucial for understanding the lubrication mechanism in articular cartilage. Thus, the inter- and intra-molecular interaction energies between the residues of mucin are analyzed. The results indicate that the mucin concentration significantly impacts its cross-linking behavior. Between 160 g/L and 214 g/L, there seems to be a critical concentration above which crowding begins to alter intermolecular interactions and their energies. This transition is further supported by the mean squared displacement of the molecules. At a high concentration, the system starts to behave subdiffusively due to network development. We also calculate a sample mean squared displacement and p-variation tests to demonstrate how the statistical nature of the dynamics is likewise altered for different concentrations

Hydrogen and Water Bonding between Glycosaminoglycans and Phospholipids in the Synovial Fluid: Molecular Dynamics Study

Synovial fluid is a lubricant of the synovial joint that shows remarkable tribological properties. These properties originate in the synergy between its components, with two of its major components, glycosaminoglycans (GAGs) and phospholipids (PLs), playing a major role in boundary and mixed lubrication regimes. All-atom molecular dynamic simulations were performed to investigate the way these components bond. Hyaluronic acid (HA) and chondroitin sulphate (CS) bonding with three types of lipids was tested. The results show that both glycosaminoglycans bind lipids at a similar rate, except for 1,2-d-ipalmitoyl-sn-glycero-3-phosphoethanolamine lipids, which bind to chondroitin at a much higher rate than to hyaluronan. The results suggest that different synovial fluid lipids may play a different role when binding to both hyaluronan and chondroitin sulphate. The presented results may help in understanding a process of lubrication of articular cartilage at a nanoscale level

Application of graphene as a nanoindenter interacting with phospholipid membranes - computer simulation study

Synthesis of graphene (GN) in 2004 stimulated wide interest inpotential applications of 2D materials in catalysis, optoelectronics, biotechnology,and construction of sensing devices. In the presented study, interactions betweenGN sheets and phospholipid bilayers are examined using steered moleculardynamics simulations. GN sheets of different sizes were inserted into a bilayer andsubsequently withdrawn from it at two different rates (1 and 2 m/s). In somecases, nanoindentation led to substantial damage of the phospholipid bilayer;however, an effective self-sealing process occurred even after significantdegradation. The average force and work, deflection of the membrane duringindentation, withdrawal processes, and structural changes caused by moving sheetsare discussed. These quantities are utilized to estimate the suitability of GN sheetsfor targeted drug delivery or other nanomedicine tools. The results are comparedwith those obtained for other nanostructures such as homogeneous andheterogeneous nanotubes

Steered molecular dynamics of lipid membrane indentation by carbon and silicon-carbide nanotubes - the impact of indenting angle uncertainty

Due to the semi-liquid nature and uneven morphologies of biological membranes, indentation may occur in a range of non-ideal conditions. These conditions are relatively unstudied and may alter the physical characteristics of the process. One of the basic challenges in the construction of nanoindenters is to appropriately align the nanotube tip and approach the membrane at a perpendicular angle. To investigate the impact of deviations from this ideal, we performed non-equilibrium steered molecular dynamics simulations of the indentation of phospholipid membranes by homogeneous CNT and non-homogeneous SiCNT indenters. We used various angles, rates, and modes of indentation, and the withdrawal of the relative indenter out of the membrane in corresponding conditions was simulated

Albumin-hyaluronan interactions : influence of ionic composition probed by molecular dynamics

The lubrication mechanism in synovial fluid and joints is not yet fully understood. Nevertheless, intermolecular interactions between various neutral and ionic species including large macromolecular systems and simple inorganic ions are the key to understanding the excellent lubrication performance. An important tool for characterizing the intermolecular forces and their structural consequences is molecular dynamics. Albumin is one of the major components in synovial fluid. Its electrostatic properties, including the ability to form molecular complexes, are closely related to pH, solvation, and the presence of ions. In the context of synovial fluid, it is relevant to describe the possible interactions between albumin and hyaluronate, taking into account solution composition effects. In this study, the influence of Na+, Mg2+, and Ca2+ ions on human serum albumin–hyaluronan interactions were examined using molecular dynamics tools. It was established that the presence of divalent cations, and especially Ca2+, contributes mostly to the increase of the affinity between hyaluronan and albumin, which is associated with charge compensation in negatively charged hyaluronan and albumin. Furthermore, the most probable binding sites were structurally and energetically characterized. The indicated moieties exhibit a locally positive charge which enables hyaluronate binding (direct and water mediated)

Influence of the molecular weight and the presence of calcium ions on the molecular interaction of hyaluronan and DPPC

Hyaluronan is an essential physiological bio macromolecule with di erent functions. One prominent area is the synovial fluid which exhibits remarkable lubrication properties. However, the synovial fluid is a multi-component system where di erent macromolecules interact in a synergetic fashion. Within this study we focus on the interaction of hyaluronan and phospholipids, which are thought to play a key role for lubrication. We investigate how the interactions and the association structures formed by hyaluronan (HA) and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) are influenced by the molecular weight of the bio polymer and the ionic composition of the solution. We combine techniques allowing us to investigate the phase behavior of lipids (di erential scanning calorimetry, zeta potential and electrophoretic mobility) with structural investigation (dynamic light scattering, small angle scattering) and theoretical simulations (molecular dynamics). The interaction of hyaluronan and phospholipids depends on the molecular weight, where hyaluronan with lower molecular weight has the strongest interaction. Furthermore, the interaction is increased by the presence of calcium ions. Our simulations show that calcium ions are located close to the carboxylate groups of HA and, by this, reduce the number of formed hydrogen bonds between HA and DPPC. The observed change in the DPPC phase behavior can be attributed to a local charge inversion by calcium ions binding to the carboxylate groups as the binding distribution of hyaluronan and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine is not changed