Clotting Phenomena at the Blood-Polymer Interface and Development of Blood Compatible Polymeric Surfaces

In the past two decades many attempts have been made to relate surface and interfacial parameters with the blood compatibility of polymeric surfaces. It is however doubtful if by a single parameter the behaviour of blood on a surface can be predicted. Two major aspects of blood compatibility - the prevention of platelet adhesion and the deactivation of the intrinsic coagulation system are determined by the measure and nature of competitive blood protein adsorption on the foreign surface. The adhesion of blood platelets is promoted by adsorbed fibrinogen and gamma globulin, while adsorbed albumin inhibits platelet adhesion. Heparinised surfaces do not adsorb fibrin and consequently no adhesion of platelets takes place. Other surfaces with low platelet adhesion are the hydrogels, certain block copolyetherurethanes, polyelectrolyte complexes and biolised proteins. Heparinised surfaces of the cationically bonded type inhibit the intrinsic coagulation as well, however this may be due to unstable coatings and heparin leakage. \ud In the authors laboratory a synthetic heparinoid was prepared with the structure - [CH2 - C(CH3 NHSO3 Na - C(H) COONa - CH2 -]x with Mw = (7.5 /pm 1.0) × 105 and an in vivo anticoagulant activity of 50% of heparin. Its coatings on PVC, using tridodecylmethyl-ammonium chloride as a coupling agent, are stable in plasma and salt solutions and provide surfaces which show negligible platelet adhesion and a strong inhibition of the intrinsic coagulation on contact with blood. Similar results were found with polydimethylsiloxane surfaces coated with this heparinoid

The role of cell-cell adhesion in wound healing

We present a stochastic model which describes fronts of cells invading a wound. In the model cells can move, proliferate, and experience cell-cell adhesion. We find several qualitatively different regimes of front motion and analyze the transitions between them. Above a critical value of adhesion and for small proliferation large isolated clusters are formed ahead of the front. This is mapped onto the well-known ferromagnetic phase transition in the Ising model. For large adhesion, and larger proliferation the clusters become connected (at some fixed time). For adhesion below the critical value the results are similar to our previous work which neglected adhesion. The results are compared with experiments, and possible directions of future work are proposed.Comment: to appear in Journal of Statistical Physic

The Influence of Substrate Structure on Membrane Adhesion

We consider a membrane both weakly and strongly adhering to a geometrically structured substrate. The interaction potential is assumed to be local, via the Deryagin approximation, and harmonic. Consequently, we can analytically describe a variety of different geometries: as well as randomly rough self-affine surfaces, smooth substrates interrupted by an isolated cylindrical pit, a single elongated trench or a periodic array of trenches are investigated. We present more general expressions for the adhesion energy and membrane configuration in Fourier space and find that, compared to planar surfaces, the adhesion energy decreases. We also highlight the possibility of overshoots occurring in the membrane profile and look at its degree of penetration into surface indentations.Comment: 41 pages LaTex, 12 EPS figure

Numerical analysis of a mechanotransduction dynamical model reveals homoclinic bifurcations of extracellular matrix mediated oscillations of the mesenchymal stem cell fate

We perform one and two-parameter numerical bifurcation analysis of a mechanotransduction model approximating the dynamics of mesenchymal stem cell differentiation into neurons, adipocytes, myocytes and osteoblasts. For our analysis, we use as bifurcation parameters the stiffness of the extracellular matrix and parameters linked with the positive feedback mechanisms that up-regulate the production of the YAP/TAZ transcriptional regulators (TRs) and the cell adhesion area. Our analysis reveals a rich nonlinear behaviour of the cell differentiation including regimes of hysteresis and multistability, stable oscillations of the effective adhesion area, the YAP/TAZ TRs and the PPAR$\gamma$ receptors associated with the adipogenic fate, as well as homoclinic bifurcations that interrupt relatively high-amplitude oscillations abruptly. The two-parameter bifurcation analysis of the Andronov-Hopf points that give birth to the oscillating patterns predicts their existence for soft extracellular substrates ($<1kPa$), a regime that favours the neurogenic and the adipogenic cell fate. Furthermore, in these regimes, the analysis reveals the presence of homoclinic bifurcations that result in the sudden loss of the stable oscillations of the cell-substrate adhesion towards weaker adhesion and high expression levels of the gene encoding Tubulin beta-3 chain, thus favouring the phase transition from the adipogenic to the neurogenic fate

Estimation of the solubility parameters of model plant surfaces and agrochemicals: a valuable tool for understanding plant surface interactions

Background Most aerial plant parts are covered with a hydrophobic lipid-rich cuticle, which is the interface between the plant organs and the surrounding environment. Plant surfaces may have a high degree of hydrophobicity because of the combined effects of surface chemistry and roughness. The physical and chemical complexity of the plant cuticle limits the development of models that explain its internal structure and interactions with surface-applied agrochemicals. In this article we introduce a thermodynamic method for estimating the solubilities of model plant surface constituents and relating them to the effects of agrochemicals. Results Following the van Krevelen and Hoftyzer method, we calculated the solubility parameters of three model plant species and eight compounds that differ in hydrophobicity and polarity. In addition, intact tissues were examined by scanning electron microscopy and the surface free energy, polarity, solubility parameter and work of adhesion of each were calculated from contact angle measurements of three liquids with different polarities. By comparing the affinities between plant surface constituents and agrochemicals derived from (a) theoretical calculations and (b) contact angle measurements we were able to distinguish the physical effect of surface roughness from the effect of the chemical nature of the epicuticular waxes. A solubility parameter model for plant surfaces is proposed on the basis of an increasing gradient from the cuticular surface towards the underlying cell wall. Conclusions The procedure enabled us to predict the interactions among agrochemicals, plant surfaces, and cuticular and cell wall components, and promises to be a useful tool for improving our understanding of biological surface interactions

Kinetic Monte Carlo and Cellular Particle Dynamics Simulations of Multicellular Systems

Computer modeling of multicellular systems has been a valuable tool for interpreting and guiding in vitro experiments relevant to embryonic morphogenesis, tumor growth, angiogenesis and, lately, structure formation following the printing of cell aggregates as bioink particles. Computer simulations based on Metropolis Monte Carlo (MMC) algorithms were successful in explaining and predicting the resulting stationary structures (corresponding to the lowest adhesion energy state). Here we present two alternatives to the MMC approach for modeling cellular motion and self-assembly: (1) a kinetic Monte Carlo (KMC), and (2) a cellular particle dynamics (CPD) method. Unlike MMC, both KMC and CPD methods are capable of simulating the dynamics of the cellular system in real time. In the KMC approach a transition rate is associated with possible rearrangements of the cellular system, and the corresponding time evolution is expressed in terms of these rates. In the CPD approach cells are modeled as interacting cellular particles (CPs) and the time evolution of the multicellular system is determined by integrating the equations of motion of all CPs. The KMC and CPD methods are tested and compared by simulating two experimentally well known phenomena: (1) cell-sorting within an aggregate formed by two types of cells with different adhesivities, and (2) fusion of two spherical aggregates of living cells.Comment: 11 pages, 7 figures; submitted to Phys Rev