Concept: Molecular diffusion
Films of ethyl cellulose (EC) and water-soluble hydroxypropyl cellulose (HPC) can be used for extended release coatings in oral formulations. The permeability and microstructure of free EC/HPC films with 30% w/w HPC were studied to investigate effects of EC molecular weight. Phase separation during film spraying and subsequent HPC leaching after immersion in aqueous media cause pore formation in such films. It was found that sprayed films were porous throughout the bulk of the film after water immersion. The molecular weight affected HPC leaching, pore morphology and film permeability; increasing the molecular weight resulted in decreasing permeability. A model to distinguish the major factors contributing to diffusion retardation in porous films showed that the trend in permeability was determined predominantly by factors associated with the geometry and arrangement of pores, independent of the diffusing species. The film with the highest molecular weight did, however, show an additional contribution from pore wall/permeant interactions. In addition, rapid drying and increasing molecular weight resulted in smaller pores, which suggest that phase separation kinetics affects the final microstructure of EC/HPC films. Thus, the molecular weight influences the microstructural features of pores, which are crucial for mass transport in EC/HPC films.
Nanofibrillar cellulose (NFC) (also referred to as cellulose nanofibers, nanocellulose, microfibrillated, or nanofibrillated cellulose) has recently gotten wide attention in various research areas and it has also been studied as excipient in formulation of the pharmaceutical dosage forms. Here, we have evaluated the interactions between NFC and the model drugs of different structural characteristics (size, charge, etc.). The series of permeation studies were utilized to evaluate the ability of the drugs in solution to diffuse through the thin, porous, dry NFC films. An incubation method was used to determine capacity of binding of chosen model drugs to NFC as well as isothermal titration calorimetry (ITC) to study thermodynamics of the binding process. A genetically engineered fusion protein carrying double cellulose binding domain was used as a positive control since its affinity and capacity of binding for NFC have already been reported. The permeation studies revealed the size dependent diffusion rate of the model drugs through the NFC films. The results of both, binding and ITC studies showed that the studied drugs bind to the NFC material and indicated the pH dependence of the binding and electrostatic forces as the main mechanism.
High-speed tracking of single particles is a gateway to understanding physical, chemical, and biological processes at the nanoscale. It is also a major experimental challenge, particularly for small, nanometer-scale particles. Although methods such as confocal or fluorescence microscopy offer both high spatial resolution and high signal-to-background ratios, the fluorescence emission lifetime limits the measurement speed, while photobleaching and thermal diffusion limit the duration of measurements. Here we present a tracking method based on elastic light scattering that enables long-duration measurements of nanoparticle dynamics at rates of thousands of frames per second. We contain the particles within a single-mode silica fiber containing a sub-wavelength, nano-fluidic channel and illuminate them using the fiber’s strongly confined optical mode. The diffusing particles in this cylindrical geometry are continuously illuminated inside the collection focal plane. We show that the method can track unlabeled dielectric particles as small as 20 nm as well as individual cowpea chlorotic mottle virus (CCMV) virions - 4.6 megadaltons in size - at rates of over 3 kHz for durations of tens of seconds. Our setup is easily incorporated into common optical microscopes and extends their detection range to nanometer-scale particles and macromolecules. The ease-of-use and performance of this technique support its potential for widespread applications in medical diagnostics and micro total analysis systems.
Heterocyst-forming cyanobacteria grow as filaments in which intercellular molecular exchange takes place. During the differentiation of N2-fixing heterocysts, regulators are transferred between cells. In the diazotrophic filament, vegetative cells that fix CO2 through oxygenic photosynthesis provide the heterocysts with reduced carbon and heterocysts provide the vegetative cells with fixed nitrogen. Intercellular molecular transfer has been traced with fluorescent markers, including calcein, 5-carboxyfluorescein, and the sucrose analogue esculin, which are observed to move down their concentration gradient. In this work, we used fluorescence recovery after photobleaching (FRAP) assays in the model heterocyst-forming cyanobacterium Anabaena sp. strain PCC 7120 to measure the temperature dependence of intercellular transfer of fluorescent markers. We find that the transfer rate constants are directly proportional to the absolute temperature. This indicates that the “septal junctions” (formerly known as “microplasmodesmata”) linking the cells in the filament allow molecular exchange by simple diffusion, without any activated intermediate state. This constitutes a novel mechanism for molecular transfer across the bacterial cytoplasmic membrane, in addition to previously characterized mechanisms for active transport and facilitated diffusion. Cyanobacterial septal junctions are functionally analogous to the gap junctions of metazoans.
- Proceedings of the National Academy of Sciences of the United States of America
- Published about 3 years ago
The exchange of nutrients and dissolved gasses between corals and their environment is a critical determinant of the growth of coral colonies and the productivity of coral reefs. To date, this exchange has been assumed to be limited by molecular diffusion through an unstirred boundary layer extending 1-2 mm from the coral surface, with corals relying solely on external flow to overcome this limitation. Here, we present direct microscopic evidence that, instead, corals can actively enhance mass transport through strong vortical flows driven by motile epidermal cilia covering their entire surface. Ciliary beating produces quasi-steady arrays of counterrotating vortices that vigorously stir a layer of water extending up to 2 mm from the coral surface. We show that, under low ambient flow velocities, these vortices, rather than molecular diffusion, control the exchange of nutrients and oxygen between the coral and its environment, enhancing mass transfer rates by up to 400%. This ability of corals to stir their boundary layer changes the way that we perceive the microenvironment of coral surfaces, revealing an active mechanism complementing the passive enhancement of transport by ambient flow. These findings extend our understanding of mass transport processes in reef corals and may shed new light on the evolutionary success of corals and coral reefs.
Information spreading in online social communities has attracted tremendous attention due to its utmost practical values in applications. Despite that several individual-level diffusion data have been investigated, we still lack the detailed understanding of the spreading pattern of information. Here, by comparing information flows and social links in a blog community, we find that the diffusion processes are induced by three different spreading mechanisms: social spreading, self-promotion and broadcast. Although numerous previous studies have employed epidemic spreading models to simulate information diffusion, we observe that such models fail to reproduce the realistic diffusion pattern. In respect to users behaviors, strikingly, we find that most users would stick to one specific diffusion mechanism. Moreover, our observations indicate that the social spreading is not only crucial for the structure of diffusion trees, but also capable of inducing more subsequent individuals to acquire the information. Our findings suggest new directions for modeling of information diffusion in social systems, and could inform design of efficient propagation strategies based on users behaviors.
In living cells, most proteins diffuse over distances of micrometres within seconds. Protein translocation is constrained due to the cellular organization into subcompartments that impose diffusion barriers and guide enzymatic activities to their targets. Here, we introduce an approach to retrieve structural features from the scale-dependent mobility of green fluorescent protein monomer and multimers in human cells. We measure protein transport simultaneously between hundreds of positions by multi-scale fluorescence cross-correlation spectroscopy using a line-illuminating confocal microscope. From these data we derive a quantitative model of the intracellular architecture that resembles a random obstacle network for diffusing proteins. This topology partitions the cellular content and increases the dwell time of proteins in their local environment. The accessibility of obstacle surfaces depends on protein size. Our method links multi-scale mobility measurements with a quantitative description of intracellular structure that can be applied to evaluate how drug-induced perturbations affect protein transport and interactions.
A comprehensive understanding of molecular transport within nanoporous materials remains elusive in a broad variety of engineering and biomedical applications. Here, experiments and atomistic simulations are synergically used to elucidate the non-trivial interplay between nanopore hydrophilicity and surface barriers on the overall water transport through zeolite crystals. At these nanometre-length scales, these results highlight the dominating effect of surface imperfections with reduced permeability on the overall water transport. A simple diffusion resistance model is shown to be sufficient to capture the effects of both intracrystalline and surface diffusion resistances, thus properly linking simulation to experimental evidence. This work suggests that future experimental work should focus on eliminating/overcoming these surface imperfections, which promise an order of magnitude improvement in permeability.
The reactivity, speciation and solvation structure of CO2 in carbonate melts are relevant for both the fate of carbon in deep geological formations and for its electroreduction to CO (to be used as fuel) when solvated in a molten carbonate electrolyte. In particular, the high solubility of CO2 in carbonate melts has been tentatively attributed to the formation of the pyrocarbonate anion, C2O5(2-). Here we study, by first-principles molecular dynamics simulations, the behaviour of CO2 in molten calcium carbonate. We find that pyrocarbonate forms spontaneously and the identity of the CO2 molecule is quickly lost through O(2-) exchange. The transport of CO2 in this molten carbonate thus occurs in a fashion similar to the Grotthuss mechanism in water, and is three times faster than molecular diffusion. This shows that Grotthuss-like transport is more general than previously thought.
With the aim of providing reliable benchmark values, we have measured the Soret, thermodiffusion and molecular diffusion coefficients for the ternary mixture formed by 1,2,3,4-tetrahydronaphthalene, isobutylbenzene and n-dodecane for a mass fraction of 0.8-0.1-0.1 and at a temperature of 25°C. The experimental techniques used by the six participating laboratories are Optical Digital Interferometry, Taylor Dispersion technique, Open Ended Capillary, Optical Beam Deflection, Thermogravitational technique and Sliding Symmetric Tubes technique in ground conditions and Selectable Optical Diagnostic Instrument (SODI) in microgravity conditions. The measurements obtained in the SODI installation have been analyzed independently by four laboratories. Benchmark values are proposed for the thermodiffusion and Soret coefficients and for the eigenvalues of the diffusion matrix in ground conditions, and for Soret coefficients in microgravity conditions.