A molecular dynamics simulation has been performed on a synthetic membrane-spanning ion channel, consisting of four α-helical peptides, each of which is composed of the sequence Ac-(LSLLLSL)3-CONH2. In the present simulation, the channel was initially assembled dynamically as a parallel bundle in the octane portion of a phase separated water/octane system, which provided a membrane-mimetic environment, without imposing any structural constraints. After more than one nanosecond, the four helices were found to adopt an associated dimer state with two-fold symmetry, which after a further 3 ns evolved to a coiled-coil tetrameric structure with a left-handed twist. Based on the simulation, we proposed a phenomenological model to describe the two-states of the channel.

Poly[bis(trifluoroethoxy)phosphazene] (PTFEP) with a high purity and high molar mass is a biocompatible material [1] used as bulk material in medical implants. We developed a process to coat surfaces with PTFEP films and performed ELISA experiments designed to understand their blood compatibility. We observed that PTFEP adsorbs preferentially albumin from plasma, and only small amounts of coagulation or inflammation stimulating proteins. In general, there is a good correlation between increasing content of albumin in the adsorbed protein film and reduced platelet adhesion. Another important prerequisite of blood compatibility is the stabilization of the native state of adsorbed proteins, since denaturated proteins stimulate platelet adhesion. The elutability of adsorbed proteins by sodiumdodecylsulfate solution was used to quantify the amount of irreversible attached and presumably denaturated proteins. PTFEP showed a low amount of irreversibly adsorbed proteins of the coagulation cascade. Circular dichroism measurements of adsorbed fibrinogen and albumin showed only weak distortions of the secondary structure of these proteins on the surface of PTFEP.

We conclude that PTFEP has a unique blood compatibility because of the favorable composition and the stabilization of the protein layer against denaturation.

Hollow tubular structures of tyrocidines, a cyclic decapeptide with two amino acids residues in the D-configuration and eight in the L-configuration, were formed in acid aqueous solutions in the presence of ethanol (20°C). Discrete nanotubes can be produced under controlled conditions, e.g. the amount of water added, or in the presence of protons from ethanol-water solutions (45/55 %v/v). These cyclic oligopeptides crystallize into tubular structures hundreds of nanometer long with an internal diameter of 9.0 Å and outer diameter of 35 Å. Support for the proposed tubular structure is provided by electronmicroscopy, SAXS and Fourier-transform infrared spectroscopy. These structures are open-ended, having a uniform shape and constant internal diameter.

Extrusion freeform fabrication is a 3-D layerwise writing technique for forming objects directly under the control of a CAD program. This method is one of a family of rapid prototyping methods which include stereolithography, selective laser sintering and fused deposition modeling. This system can be used to build shapes, layer by layer, from hydrogels of agarose, polyacrylamide or other cross-linked water-soluble acrylic polymers.

Mineralization can be induced in these gels by building a part with alternating layers of gels containing calcium and carbonate or phosphate that can be formed into stacks which then mineralize by cross-diffusion. The write head can be conceived of as a cell which delivers the appropriate minerals to a site within a swollen gel matrix. This diffusive mineralization process can thus be compared with bone mineralization. The gel structure controls the morphology of the mineral. The site of mineralization is controlled by osmotic forces which localize most of the mineral in whichever zone has the higher ionic strength. The mineral content, expressed as a fraction of the polymer content, is similar to that of bone but the water content is much higher than in bone. This raises the question of what process drives the water exclusion during bone mineralization.

Through the use of solubilizing agents, simple salt metathesis reactions may be translated from aqueous solution to the milieu of organic solvents. When applied to the crystallization of calcium carbonate through the reaction of calcium chloride with sodium bicarbonate in “complexation-mediated” crystallization leads to the selective formation of a metastable phase, vaterite, rather than to calcite, the phase obtained from aqueous solution. Impacts on the formation of the third anhydrous phase of calcium carbonate, aragonite, are also noted. These studies suggest an additional mechanism whereby Nature may control the morphology and phase of the calcium carbonate biominerals.

Transmission electron microscopy of otoliths from the inner ear of arctic charr and pike has revealed the presence of fine banding on the scale of several nanometers. The thickness of the bands was observed to vary in different portions of the sample, and some areas were not banded. EDS analysis could not detect chemical differences within the bands, but electron diffraction showed that the crystallographic orientation of the bands is related by a lattice mismatch indicative of a twinning relationship. Previously, banding on the scale of 50 to 100 microns was observed by SEM in otoliths from arctic charr and was attributed to seasonal variations in growth. The fine-scale twinning observed in this study, however, is unlikely to be nucleated through daily variations. Electron diffraction from the pike samples shows that the material is composed of CaCO3 having the both the vaterite and aragonite structure, and hydrous CaCO3 was also observed.

The interaction of the electron beam with the sample material was investigated by conducting several electron-irradiation experiments. The electron beam was observed to interact strongly with the sample and caused the precipitation of cubic CaO from the calcium carbonate matrix. Bright-field imaging showed the development of fine grained (∼ 5 nm) randomly-oriented crystallites which accumulated with increasing electron dose. These initial results suggest that the precipitation of GaO is not driven by electron-beam heating. Previously, a similar phase-change phenomenon has been observed in hydroxyapatite from dental enamel. Other Ca-bearing biominerals may therefore also be expected to be sensitive to electron irradiation.

The cellular microstructure of insect scales can be detailed intricately with threedimensional structures and multiple thin-film layers. In butterflies, iridescent scales can reflect bright colors through thin-film interference and other optical phenomena; the balance of radiation is absorbed for thermoregulatory purposes. Results of numerical and experimental investigations into the function, properties, and structure of these scales are presented. Of particular interest are the numerical modeling of the microscale radiative effects in the scales, determining the optical properties of the biological material, and the cellular development of thin-film structures.

We describe how axonal differentiation during neuronal growth is dependent on intracellular transport. The interaction of diffusion and active transport of a morphogen whose concentration at the neurite tips influences the growth rate can lead to an instability involving winner-take-all growth, forming a single, quickly growing neurite (the axon) and inhibiting the growth of the other neurites. We discuss the dynamics of this process and its dependence on cell parameters.

A new technique for determining cellular viscosity has been developed based on two-photon excitation and fluorescence correlation spectroscopy. We have applied this method to map intracellular diffusion coefficient of small molecules at selected cytoplasmic locations of mouse fibroblast cells. The cytoplasmic diffusion rate is one tenth of that in an aqueous environment.

Ligand binding is an essential step in many biological and biochemical processes, notably protein activation. In many cases, the binding rates are determined by competition: blockers competing with ligands or decoys competing with receptors. Often, the diffusivities of the various species also play a key role. The usual modelling of these processes, however, either involves well-mixed systems, for which spatial variations are neglected, or steady-state situations for which all time evolution has ceased. The model presented here can instead account for the spatial variations that originate as a consequence of inhomogeneous initial conditions and localized binding sites. It describes their evolution in time due to a combination of mechanisms of diffusion, competition and reaction. The model, which is formulated in terms of a coupled system of equations for the probability densities of the various populations, is easy to adapt to different specific conditions and is particularly well suited for numerical calculations, e.g., on a parallel computer. Since it yields concrete predictions, it can be readily used to predict the concentrations and distributions of the various species that are needed to obtain prescribed responses.

We study theoretically phospholipid vesicle locomotion caused by adhesion. The problem is solved numerically, and an analytical solution is obtained in a perturbative scheme. The analytical result reproduces the numerical one. We provide an expression for the drift velocity as a function of relevant parameters when only local dissipation is present. We briefly discuss the transition from sliding to rolling when hydrodynamics are included. We mention situations where the vesicle may itself establish an adhesion gradient. We propose some simple experimental protocols.

Import (endocytosis) and export (secretion) of molecules from the cells is mediated by vesicles (lysosomes, endosomes) sliding along microtubules or actin filaments. These vesicles share a common feature: an internal pH of about 5, with an inner protons concentration 1000 fold higher than in the surrounding cytoplasm. As the proton gradient in mitochondria is able to drive ATP synthesis we can expect a similar role (energy supplier) for protons in all acidic vesicles. To experimentally test the vesicles' transport we have loaded them with a fluorescent dye (chloroquine) and then measured its efflux over 5 hours. This efflux was reduced by all treatments lowering the actual concentration of protons in the vesicles, independently of the properties. Treatments included lowering intracellular NADH, inhibitors of ATP-dependent proton translocase and/or the Na+/H+antiport, drugs that accumulate into lysosomes, buffering its acidity (chloroquine, doxorubicin). These results support the idea of a role of a proton gradient as a fuel for protein motors.

Normal endothelial cells (ECs), lining the blood vessels, are influenced by their interaction with the underlying potentially piezoelectric extracellular matrix (ECM). That this interaction may affect the EC metabolic state and functions in vivo prompted us to study the subsequent response of cultured ECs on indium-tin oxide (ITO) glass electrodes subjected to 1 hr of constant DC surface potential ranging from -0.3 to +0.6 V (vs. Ag/AgCl). We measured, relative to controls, cellular viability, growth rate and changes in actin microfilament organization in ECs over a subsequent 6 days in culture. The growth rate of ECs was stimulated by negative potential and inhibited by positive potential. Differences could be detected as early as three days post-potential. We also observed a potential dependent cellular shape change and actin microfilament rearrangement at positive potentials within four days of treatment. ECs changed in average cell surface area and assumed a polygonal cell shape in response to treatment. Using NBD-phalloidin stain for actin and fluorescence microscopy, microfilaments were observed to re-distribute to the periphery of the cell at positive potential, indicative of cellular stress.

A master equation formalism is used to model the growth and metastasis of a tumor as a function of the diffusion and absorption of a nutrient. Healthy and cancerous (C-) cells compete to bind the nutrient, which is allowed to diffuse starting from a prescribed region. Two thresholds are defined for the quantity of nutrient bound by the C-cells. If this quantity falls below the lower threshold, the cell dies, while if it increases above the upper threshold, the cell divides according to a predefined stochastic mechanism. C-cells migrate when they record a low concentration of free nutrient in the local environment. The model is formulated in terms of a coupled system of equations for the cell populations and the free and bound nutrient. This system can be solved by using the Local Interaction Simulation Approach (LISA), a numerical procedure that permits an efficient and detailed solution and is easily adaptable to parallel processing. With suitable parameter variation, the model can describe multiple tumor configurations, ranging from the classical spheroid with a necrotic core favored by mathematicians to very anisotropic shapes with inhomogeneous concentrations of the various populations. This is important because the nature of the anisotropy may be crucial in determining whether and how the cancer metastasizes. The effects of stochasticity and the presence of additional nutrients or inhibitors can be easily incorporated.