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.
Exposed to ionizing radiation, nanomaterials often undergo unusual transformations compared to their bulk form. However, atomic-level mechanisms of such transformations are largely unknown. This work visualizes and quantifies nanopore shrinkage in nanoporous alumina subjected to low-energy ion beams in a helium ion microscope. Mass transport in porous alumina is thus simultaneously induced and imaged with nanoscale precision, thereby relating nanoscale interactions to mesoscopic deformations. The interplay between chemical bonds, disorders, and ionization-induced transformations is analyzed. It is found that irradiation-induced diffusion is responsible for mass transport and that the ionization affects mobility of diffusive entities. The extraordinary room temperature superplasticity of the normally brittle alumina is discovered. These findings enable the effective manipulation of chemical bonds and structural order by nanoscale ion-matter interactions to produce mesoscopic structures with nanometer precision, such as ultra-high density arrays of sub-10-nm pores with or without the accompanying controlled plastic deformations.
Decreases in Maximal Oxygen Uptake Following Long-duration Spaceflight: Role of Convective and Diffusive O2 Transport Mechanisms
- Journal of applied physiology (Bethesda, Md. : 1985)
- Published over 1 year ago
We have previously predicted that the decrease in maximal oxygen uptake (VO2max) that accompanies time in microgravity reflects decrements in both convective and diffusive O2 transport to the mitochondria of the contracting myocytes. The aim of this investigation was therefore to quantify the relative changes in convective O2 transport (QO2) and O2 diffusing capacity (DO2) following long duration spaceflight. In 9 astronauts, resting hemoglobin concentration ([Hb]), VO2max, maximal cardiac output (QTmax), and differences in arterial and venous O2 contents (CaO2-CvO2) were obtained retrospectively for International Space Station Increments 19 through 33 (April 2009-November 2012). QO2 and DO2 were calculated from these variables via integration of Fick’s Principle of Mass Conservation and Fick’s Law of Diffusion. VO2max significantly decreased from pre- to post-flight (-53.9 ± 45.5%, P =0.008). The significant decrease in Q ̇_Tmax (-7.8±9.1%, P =0.05), despite an unchanged [Hb] resulted in a significantly decreased QO2 (-11.4±10.5%, P = 0.02). DO2 significantly decreased from pre- to post-flight by -27.5±24.5% (P =0.04), as did the peak CaO2-CvO2 (-9.2±7.5%, P =0.007). Using linear regression analysis, changes in VO2max were significantly correlated with changes in DO2 (R2=0.47; P = 0.04). These data suggest that space flight decreases both convective and diffusive O2 transport. These results have practical implications for future long-duration space missions and highlight the need to resolve the specific mechanisms underlying these spaceflight-induced changes along the O2 transport pathway.
Macromolecular diffusion in homogeneous fluid at length scales greater than the size of the molecule is regarded as a random process. The mean-squared displacement (MSD) of molecules in this regime increases linearly with time. Here we show that non-random motion of DNA molecules in this regime that is undetectable by the MSD analysis can be quantified by characterizing the molecular motion relative to a latticed frame of reference. Our lattice occupancy analysis reveals unexpected sub-modes of motion of DNA that deviate from expected random motion in the linear, diffusive regime. We demonstrate that a subtle interplay between these sub-modes causes the overall diffusive motion of DNA to appear to conform to the linear regime. Our results show that apparently random motion of macromolecules could be governed by non-random dynamics that are detectable only by their relative motion. Our analytical approach should advance broad understanding of diffusion processes of fundamental relevance.
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.
- Proceedings of the National Academy of Sciences of the United States of America
- Published over 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.
Scanning Fluorescence Correlation Spectroscopy (scanning FCS) is a variant of conventional point FCS that allows molecular diffusion at multiple locations to be measured simultaneously. It enables disclosure of potential spatial heterogeneity in molecular diffusion dynamics and also the acquisition of a large amount of FCS data at the same time, providing large statistical accuracy. Here, we optimize the processing and analysis of these large-scale acquired sets of FCS data. On one hand we present FoCuS-scan, scanning FCS software that provides an end-to-end solution for processing and analysing scanning data acquired on commercial turnkey confocal systems. On the other hand, we provide a thorough characterisation of large-scale scanning FCS data over its intended time-scales and applications and propose a unique solution for the bias and variance observed when studying slowly diffusing species. Our manuscript enables researchers to straightforwardly utilise scanning FCS as a powerful technique for measuring diffusion across a broad range of physiologically relevant length scales without specialised hardware or expensive software.
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.
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.