A mathematical insight in the epithelial-mesenchymal-like transition in cancer cells and its effect in the invasion of the extracellular matrix

Current biological knowledge supports the existence of a secondary group of cancer cells within the body of the tumour that exhibits stem cell-like properties. These cells are termed Cancer Stem Cells (CSCs}, and as opposed to the more usual Differentiated Cancer Cells (DCCs), they exhibit higher motility, they are more resilient to therapy, and are able to metastasize to secondary locations within the organism and produce new tumours. The origin of the CSCs is not completely clear; they seem to stem from the DCCs via a transition process related to the Epithelial-Mesenchymal Transition (EMT) that can also be found in normal tissue. In the current work we model and numerically study the transition between these two types of cancer cells, and the resulting "ensemble" invasion of the extracellular matrix. This leads to the derivation and numerical simulation of two systems: an algebraic-elliptic system for the transition and an advection-reaction-diffusion system of Keller-Segel taxis type for the invasion

Peptide–liposome association. A critical examination with mastoparan-X

AbstractMastoparan-X, a wasp venom factor, is a membrane active peptide whose binding to lipid vesicles is of basic interest towards an analysis of its functions. Titration of aqueous peptide solutions with liposomes allows the determination of the association isotherm, i.e. a plot of bound peptide per lipid versus the free peptide concentration. We have scrutinised the various steps in the evaluation procedure, considering circular dichroism as well as fluorescence intensity as possible signals for the binding process. First of all the measured data had to be corrected for light scattering effects which may otherwise appreciably falsify the final results. Uncertainties due to inherent difficulties regarding the reproducibility of lipid preparations and inevitable titration errors have to be considered. The consequences of these errors for the quantitative analysis of the titration curves were investigated. The plotted curves can be reasonably well fitted by a functional relationship derived from a Gouy–Chapman model approach that assumes a partitioning of monomeric peptide. The two relevant parameters, partition coefficient and effective charge number, and their error ranges have been determined for mastoparan-X and a series of phosphatidylcholine vesicle sizes and various ionic strengths. These findings show that the applied analysis implies a sufficient basis for calculations of the amount of lipid bound peptide in practice. However, the possible existence of peptide aggregates cannot generally be excluded from a formal monomer associated curve fit as indicated by computer simulations

Numerical study of cancer cell invasion dynamics using adaptive mesh refinement: the urokinase model

In the present work we investigate the chemotactically and proteolytically driven tissue invasion by cancer cells. The model employed is a system of advection-reaction-diffusion equations that features the role of the serine protease urokinase-type plasminogen activator. The analytical and numerical study of this system constitutes a challenge due to the merging, emerging, and travelling concentrations that the solutions exhibit. Classical numerical methods applied to this system necessitate very fine discretization grids to resolve these dynamics in an accurate way. To reduce the computational cost without sacrificing the accuracy of the solution, we apply adaptive mesh refinement techniques, in particular h-refinement. Extended numerical experiments exhibit that this approach provides with a higher order, stable, and robust numerical method for this system. We elaborate on several mesh refinement criteria and compare the results with the ones in the literature. We prove, for a simpler version of this model, $L^\infty$ bounds for the solutions, we study the stability of its conditional steady states, and conclude that it can serve as a test case for further development of mesh refinement techniques for cancer invasion simulations

Untersuchung zur Anwendung elektrooptischer Messungen für die Detektion von strahleninduzierten Einzelstrangbrüchen an Plasmid-DNA

Ruprecht-Karls-Universität Heidelberg, Diplom, 199

Molluscan mega-hemocyanin: an ancient oxygen carrier tuned by a ~550 kDa polypeptide

<p>Abstract</p> <p>Background</p> <p>The allosteric respiratory protein hemocyanin occurs in gastropods as tubular di-, tri- and multimers of a 35 × 18 nm, ring-like decamer with a collar complex at one opening. The decamer comprises five subunit dimers. The subunit, a 400 kDa polypeptide, is a concatenation of eight paralogous functional units. Their exact topology within the quaternary structure has recently been solved by 3D electron microscopy, providing a molecular model of an entire didecamer (two conjoined decamers). Here we study keyhole limpet hemocyanin (KLH2) tridecamers to unravel the exact association mode of the third decamer. Moreover, we introduce and describe a more complex type of hemocyanin tridecamer discovered in fresh/brackish-water cerithioid snails (<it>Leptoxis</it>, <it>Melanoides</it>, <it>Terebralia</it>).</p> <p>Results</p> <p>The "typical" KLH2 tridecamer is partially hollow, whereas the cerithioid tridecamer is almost completely filled with material; it was therefore termed "mega-hemocyanin". In both types, the staggering angle between adjoining decamers is 36°. The cerithioid tridecamer comprises two typical decamers based on the canonical 400 kDa subunit, flanking a central "mega-decamer" composed of ten unique ~550 kDa subunits. The additional ~150 kDa per subunit substantially enlarge the internal collar complex. Preliminary oxygen binding measurements indicate a moderate hemocyanin oxygen affinity in <it>Leptoxis </it>(p50 ~9 mmHg), and a very high affinity in <it>Melanoides </it>(~3 mmHg) and <it>Terebralia </it>(~2 mmHg). Species-specific and individual variation in the proportions of the two subunit types was also observed, leading to differences in the oligomeric states found in the hemolymph.</p> <p>Conclusions</p> <p>In cerithioid hemocyanin tridecamers ("mega-hemocyanin") the collar complex of the central decamer is substantially enlarged and modified. The preliminary O₂binding curves indicate that there are species-specific functional differences in the cerithioid mega-hemocyanins which might reflect different physiological tolerances of these gill-breathing animals. The observed differential expression of the two subunit types of mega-hemocyanin might allow individual respiratory acclimatization. We hypothesize that mega-hemocyanin is a key character supporting the adaptive radiation and invasive capacity of cerithioid snails.</p

Extraordinary stability of hemocyanins from L. polyphemus and E. californicum studied using infrared spectroscopy from 294 to 20 K

Hemocyanins are large oligomeric respiratory proteins found in many arthropods and molluscs. Here we give infrared spectroscopic evidence of a high stability towards exposure to sub-zero temperatures for hemocyanins from the arthropods Limulus polyphemus and Eurypelma californicum at different pH values. Small but distinct temperature induced changes of the secondary structure were observed, but a stable core of at least 40% α-helical structure is preserved as identified in the infrared spectra obtained between 294 and 20 K. The structural changes differ in detail somewhat for the two hemocyanins, with overall fewer changes observed in the case of E. californicum. Notably, in both cases the overall changes in the α-helical content are found to be fully reversible. The small changes in the secondary structure and reversibility upon cold treatment seem to be a particular property of the two hemocyanins, since it was not observed for myoglobin studied in the same way

PAA-PAMPS Copolymers as an Efficient Tool to Control CaCO3 Scale Formation

Dietzsch M, Barz M, Schüler T, et al. PAA-PAMPS Copolymers as an Efficient Tool to Control CaCO3 Scale Formation. Langmuir. 2013;29(9):3080-3088.Scale formation, the deposition of certain minerals such as CaCO3, MgCO3, and CaSO4 center dot 2H(2)O in industrial facilities and household devices, leads to reduced efficiency or severe damage. Therefore, incrustation is a major problem in everyday life. In recent years, double hydrophilic block copolymers (DHBCs) have been the focus of interest in academia with regard to their antiscaling potential. In this work, we synthesized well-defined blocklike PAA-PAMPS copolymers consisting of acrylic acid (AA) and 2-acrylamido-2-methyl-propane sulfonate (AMPS) units in a one-step reaction by RAFT polymerization. The derived copolymers had dispersities of 1.3 and below. The copolymers have then been investigated in detail regarding their impact on the different stages of the crystallization process of CaCO3. Ca2+ complexation, the first step of a precipitation process, and polyelectrolyte stability in aqueous solution have been investigated by potentiometric measurements, isothermal titration calorimetry (ITC), and dynamic light scattering (DLS). A weak Ca2+ induced copolymer aggregation without concomitant precipitation was observed. Nudeation, early particle growth, and colloidal stability have been monitored in situ with DLS. The copolymers retard or even completely suppress nucleation, most probably by complexation of solution aggregates. In addition, they stabilize existing CaCO3 particles in the nanometer regime. In situ AFM was used as a tool to verify the coordination of the copolymer to the calcite (104) crystal surface and to estimate its potential as a growth inhibitor in a supersaturated CaCO3 environment. All investigated copolymers instantly stopped further crystal growth. The carboxylate richest copolymer as the most promising antiscaling candidate proved its enormous potential in scale inhibition as well in an industrial-filming test (Fresenius standard method)