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An electrodynamics-based model for ion diffusion in microbial polysaccharides.

An electrodynamics-based model was formulated for simulation of ion diffusion in microbial polysaccharides. The fixed charges and electrostatic double layers that may associate with microbial polysaccharides and their effects on ion diffusion were explicitly built into the model. The model extends a common multicomponent ion diffusion formulation that is based on irreversible thermodynamics under a zero ionic charge flux condition, which is only applicable to the regions without fixed charges and electrostatic double layers. An efficient numerical procedure was presented to solve the differential equations in the model. The model well described key features of experimental observations of ion diffusion in negatively charged microbial polysaccharides including accelerated diffusive transport of cations, exclusion of anions, and increased rate of cation transport with increasing negative charge density. The simulated diffusive fluxes of cations and anions were consistent with a cation exchange diffusion concept in negatively charged polysaccharides at the interface of plant roots and soils; and the developed model allows to mathematically study such diffusion phenomena. An illustrative example was also provided to simulate dynamic behavior of ionic current during ion diffusion within a charged bacterial cell wall polysaccharide and the effects of the ionic current on the compression or expansion of the bacterial electrostatic double layer at the interface of the cell wall and bulk solution.

Cell Wall↗

Diffusion and economic consequences of health technologies in prostate cancer care in Sweden, 1991-2002.

OBJECTIVE: To describe the diffusion of six main health technologies used for management of prostate cancer, to estimate the economic consequences of technological changes, and to explore factors behind the diffusion. METHODS: Data describing the diffusion 1991-2002 were obtained from population-based databases. Costs were obtained from Linköping University Hospital and Apoteket AB. Factors affecting the diffusion of the technologies were explored. RESULTS: Utilization of technologies with a curative and/or palliative aim has increased over time, except for surgical castration. PSA-tests are used increasingly. The total cost of the study technologies has increased from 20 million euros in 1991 to 65 million euros in 2002. Classification of radical prostatectomy revealed a profile associated with a slow/limited diffusion, while classification of PSA-tests revealed a profile associated with a rapid/extensive diffusion. CONCLUSIONS: Several technological changes in the management of prostate cancer have occurred without proven benefits and have contributed to increased costs. There are other factors, besides scientific evidence, that have an impact on the diffusion. Consequently, activities aimed at facilitating an appropriate diffusion of new technologies are needed. The analytical framework used here may be helpful in identifying technologies that are likely to experience inappropriate diffusion and therefore need particular attention.

Diffusion of Innovation↗

Protein diffusion in agarose hydrogel in situ measured by improved refractive index method.

The accurate knowledge of the diffusion behavior of protein within biomimetic hydrogel matrix at body temperature has a great implication for the design of efficient controlled release protein-base drug delivery devices. In this paper, we improved our previous in situ refractive index method with great temperature-controlled capability. For the first time, this newly improved method was employed to study the diffusion of protein (bovine serum albumin (BSA) and lysozyme) in agarose hydrogel at body temperature (37 degrees C). The change of the gel refractive index caused by the change of the diffusing protein concentration within the gel during the diffusion process enables the effective diffusion coefficients of protein to be estimated. The diffusion coefficients of proteins decrease with the increase of the concentration of agarose and the solute molecular size. At the considered range of agarose concentration (0.5-3.0 wt.%), the diffusion coefficients range from 4.98 to 8.21 x 10(-7) cm(2)/s for BSA and 1.15 to 1.56 x 10(-6) cm(2)/s for lysozyme, respectively. Temperature dependence of diffusivity of BSA in agarose hydrogel was also investigated. Furthermore, the retardance effect of polymer volume fraction on the diffusivity of both BSA and lysozyme in agarose hydrogels was analyzed with three models, Amsden's, Clauge and Philips', and Ogsten's model.

Algorithms↗

Diffusion of hydrocarbons in the reforming catalyst: molecular modelling.

This is an analysis of the diffusion and adsorption of the model reagents involved in the reforming process (heptane, methylcyclohexane and toluene) in the support (gamma-Al2O3) and catalyst (Pt/gamma-Al2O3) made use of in this process. Since the properties of these catalytic systems are influenced by the interactions between the atoms of the catalyst structure (host) and the atoms of the reagents (guest), analysis was carried out at the molecular level, using advanced computer simulations (molecular dynamics and forced diffusion) implemented in the MSI Software. The virtual host-guest model constructed with this software enabled a simulation of the real reforming system (reforming catalyst-reagents) and analysis of the diffusion phenomenon in this system. The results show that the propensity of the reagents to adsorption and the host-guest interaction energy are correlated with the coefficients of diffusion. The diffusion coefficient values are lower in the catalyst than in the support, probably because of the increased adsorption at the active Pt centres. The decrease in pore diameter from 17 to 10A brings about a decrease in the diffusion coefficients not only due to steric hindrance, but also as a result of capillary condensation. The favourable influence of temperature is more distinct in models characterised by a larger pore size. This is so because molecular diffusion dominates over the mechanism of Knudsen diffusion, which increases the temperature-dependence of diffusion.

Catalysis↗

Diffusion tensor imaging of articular cartilage as a measure of tissue microstructure.

OBJECTIVE: To use diffusion tensor MR micro-imaging to observe differences in magnitude and anisotropy of water diffusion between 'healthy' cartilage and cartilage enzymatically degraded to simulate arthritic damage. METHODS: Diffusion tensor images (156 x 156 microm in-plane resolution, 2mm slice thickness) of bovine cartilage were obtained at either 4.7 or 7.0 T using pulsed field gradient spin echo sequences. The parameters determined were: maximum and mean diffusivity, direction of the maximum diffusion eigenvector with respect to the normal to the articular surface and fractional anisotropy (FA) of diffusion. RESULTS: Both maximum and mean diffusion eigenvalues were found to decrease, respectively, from approximately 1.95 x 10(-9) and 1.80 x 10(-9) m2 s(-1) at the articular surface to approximately 1.08 x 10(-9) and 0.79 x 10(-9) m2 s(-1) in the deep zone. A systematic change was observed in the direction of the eigenvector corresponding to maximum diffusivity, reflecting the expected change in orientation of the collagen macrofibrillar bundles. Degradation with trypsin to remove proteoglycans resulted in a 10-15% increase in apparent diffusion coefficient of water in the cartilage, with no apparent change in FA. CONCLUSIONS: These methods have the potential to be used to probe local changes in tissue microstructure and the hydrodynamic status of cartilage during development of osteoarthritis.

Animals↗

Molecular diffusion in sperm plasma membranes during epididymal maturation.

Fluorescence recovery after photobleaching (FRAP) analysis has been used to measure lipid diffusion in different regions of the sperm plasma membrane. Our goal has been to understand how some membrane components are confined to specific surface domains, whilst others are freely diffusing and in some cases are able to migrate against large concentration gradients. Results with a variety of fluorescent lipid reporter probes (ODAF, NBD-PC, NBD-cholesterol) show that diffusion coefficients (D) are generally three to four times higher on the sperm acrosome than on the principal piece of the tail and increase significantly during epididymal maturation (ram, mouse, goat, dog and monkey sperm). Cholesterol diffusion is approximately 10 times faster on the sperm head than the tail and has a heterogenous distribution when detected with filipin. Lipid diffusion is very temperature sensitive but remarkably insensitive to changes in external pH and osmotic pressure. There was no evidence that the posterior ring or annulus functioned as diffusion barriers to lipids. On this basis it was possible to construct models of increasing complexity to describe the behaviour of a lipid molecule on the sperm surface, beginning with simple linear diffusion progressing to random diffusion and eventually to constrained diffusion.

Animals↗

Biexponential characterization of prostate tissue water diffusion decay curves over an extended b-factor range.

Detailed measurements of water diffusion within the prostate over an extended b-factor range were performed to assess whether the standard assumption of monoexponential signal decay is appropriate in this organ. From nine men undergoing prostate MR staging examinations at 1.5 T, a single 10-mm-thick axial slice was scanned with a line scan diffusion imaging sequence in which 14 equally spaced b factors from 5 to 3,500 s/mm(2) were sampled along three orthogonal diffusion sensitization directions in 6 min. Due to the combination of long scan time and limited volume coverage associated with the multi-b-factor, multidirectional sampling, the slice was chosen online from the available T2-weighted axial images with the specific goal of enabling the sampling of presumed noncancerous regions of interest (ROIs) within the central gland (CG) and peripheral zone (PZ). Histology from prescan biopsy (n=9) and postsurgical resection (n=4) was subsequently employed to help confirm that the ROIs sampled were noncancerous. The CG ROIs were characterized from the T2-weighted images as primarily mixtures of glandular and stromal benign prostatic hyperplasia, which is prevalent in this population. The water signal decays with b factor from all ROIs were clearly non-monoexponential and better served with bi- vs. monoexponential fits, as tested using chi(2)-based F test analyses. Fits to biexponential decay functions yielded intersubject fast diffusion component fractions in the order of 0.73+/-0.08 for both CG and PZ ROIs, fast diffusion coefficients of 2.68+/-0.39 and 2.52+/-0.38 microm(2)/ms and slow diffusion coefficients of 0.44+/-0.16 and 0.23+/-0.16 um(2)/ms for CG and PZ ROIs, respectively. The difference between the slow diffusion coefficients within CG and PZ was statistically significant as assessed with a Mann-Whitney nonparametric test (P<.05). We conclude that a monoexponential model for water diffusion decay in prostate tissue is inadequate when a large range of b factors is sampled and that biexponential analyses are better suited for characterizing prostate diffusion decay curves.

Aged↗

Measurement of macromolecular diffusion coefficients in human tumors.

The diffusive transport of macromolecules in tumors is an important determinant of the delivery of many anticancer therapeutics. However, measurements of diffusive transport to date have only been performed in animal models. In this work, diffusion coefficients of BSA and IgM were measured in human tumor biopsies (cooled to 4-7 degrees C to prevent degradation) using fluorescence recovery after photobleaching. To quantify the effects of excision and cooling, the diffusion coefficient of BSA and IgM was measured in human tumor xenografts in situ and after cooling and excision. The change in diffusion coefficients before and after excision of xenografts was used to calculate in vivo diffusion coefficients in human tumors from ex vivo measurements. Using this approach, we obtained the first quantitative determinations of macromolecular diffusion coefficients in human tumors and find that the diffusion coefficients of BSA and IgM in human colon were adenocarcinomas higher than those in xenografts. This difference is consistent with lower collagen content in the accessible regions of these human tumors. These measurements allow the quantitative prediction of the diffusive transport of like-sized macromolecular therapeutics in human tumors. These measurements should help in modeling the transport of novel large MW therapeutics, and hence in estimating their distribution and efficacy in tumors.

Animals↗

Diffusion tensor imaging in medial temporal lobe epilepsy with hippocampal sclerosis.

Interictal diffusion imaging studies in patients with medial temporal lobe epilepsy (MTLE) accompanied by hippocampal sclerosis (HS) have shown an increased diffusivity in the epileptogenic hippocampus. In this study, we wanted to explore the whole brain in order to determine if MTLE could have an impact on the organization and the architecture of a large cerebral network and to identify clinical factors that could mediate diffusion abnormalities. Diffusion tensor imaging (DTI) and statistical parametric mapping of the entire brain were performed in 35 well-defined MTLE patients and in 36 healthy volunteers. SPM analyses identified three abnormal areas: an increased diffusivity was detected in the epileptic hippocampus and the ipsilateral temporal structures associated with a decreased anisotropy along the temporal lobe, a decreased diffusivity was found in the contralateral non-sclerotic hippocampus, the amygdala, and the temporal pole, and finally, a decreased anisotropy was noted ipsilaterally in posterior extratemporal regions. Duration of epilepsy, age at onset, and the frequency of generalized tonic-clonic seizures or partial complex seizures did not correlate with the presence of diffusion abnormalities. Region of interest analysis in the hippocampus/parahippocampus demonstrated a correlation between lower ipsilateral diffusivity values and occurrence of epigastric aura and between higher anisotropy values in both hemispheres and history of febrile seizures. In conclusion, this study showed that diffusion abnormalities are not restricted to the pathologic hippocampus and involve a larger network. This pattern may indirectly reflect the epileptogenic network and may be interpreted as a cause or a consequence of epilepsy.

Adult↗

Extrasynaptic volume transmission and diffusion parameters of the extracellular space.

Extrasynaptic communication between neurons or neurons and glia is mediated by the diffusion of neuroactive substances in the volume of the extracellular space (ECS). The size and irregular geometry of the diffusion channels in the ECS substantially differ not only around individual cells but also in different CNS regions and thus affect and direct the movement of various neuroactive substances in the ECS. Diffusion in the CNS is therefore not only inhomogeneous, but often also anisotropic. The diffusion parameters in adult mammals (including humans), ECS volume fraction alpha (alpha=ECS volume/total tissue volume) and tortuosity lambda (lambda(2)=free/apparent diffusion coefficient), are typically 0.20-0.25 and 1.5-1.6, respectively, and as such hinder the diffusion of neuroactive substances and water. These diffusion parameters modulate neuronal signaling, neuron-glia communication and extrasynaptic "volume" transmission. A significant decrease in ECS volume fraction and an increase in diffusion barriers (tortuosity) occur during neuronal activity and pathological states. The changes are often related to cell swelling, cell loss, astrogliosis, the rearrangement of neuronal and astrocytic processes and changes in the extracellular matrix. They are also altered during physiological states such as development, lactation and aging. Plastic changes in ECS volume, tortuosity and anisotropy significantly affect neuron-glia communication, the spatial relation of glial processes toward synapses, glutamate or GABA "spillover" and synaptic crosstalk. The various changes in tissue diffusivity occurring during many pathological states are important for diagnosis, drug delivery and treatment.

Animals↗

In vivo (31)P-NMR diffusion spectroscopy of ATP and phosphocreatine in rat skeletal muscle.

The aim of this study was to measure the diffusion of ATP and phosphocreatine (PCr) in intact rat skeletal muscle, using (31)P-NMR. The acquisition of the diffusion-sensitized spectra was optimized in terms of the signal-to-noise ratio for ATP by using a frequency-selective stimulated echo sequence in combination with adiabatic radio-frequency pulses and surface coil signal excitation and reception. Diffusion restriction was studied by measuring the apparent diffusion coefficients of ATP and PCr as a function of the diffusion time. Orientation effects were eliminated by determining the trace of the diffusion tensor. The data were fitted to a cylindrical restriction model to estimate the unbounded diffusion coefficient and the radial dimensions of the restricting compartment. The unbounded diffusion coefficients of ATP and PCr were approximately 90% of their in vitro values at 37 degrees C. The diameters of the cylindrical restriction compartment were approximately 16 and approximately 22 microm for ATP and PCr, respectively. The diameters of rat skeletal muscle fibers are known to range from 60 to 80 microm. The modelling therefore suggests that the in vivo restriction of ATP and PCr diffusion is not imposed by the sarcolemma but by other, intracellular structures with an overall cylindrical orientation.

Adenosine Triphosphate↗

Calcium diffusion in transient and steady states in muscle.

Rates of diffusion through the extracellular space of thin sheets of myocardium from the right ventricular outflow tract of kittens were estimated at 23 degrees C for 45Ca2+ and an inert reference tracer, [14C]sucrose. The myocardial sheets were mounted in an Ussing chamber and equilibrated with Tyrode solution with varied calcium concentrations, Cao. The tracers were added to one side and their concentrations on the other side measured at 5-15-min intervals for 6 h. The apparent tracer diffusion coefficient for sucrose was 1.11 +/- 0.06 X 10(-6) cm2s-1 (mean +/- SEM, n = 74), 22% of the free diffusion coefficient; the lag time before reaching a steady state provided estimates of the intratissue volume of distribution or diffusion space of 0.41 +/- 0.15 ml/ml tissue (n = 74), a value compatible with expectations for extracellular fluid space. Over the range of Cao from 0.02 to 9.0 mM, the intratissue apparent diffusion coefficient for Ca, DCa, averaged 1.65 +/- 0.10 X 10(-6) cm2s-1, n = 74, which is 21% of the free DoCa, and was not influenced by Cao. Because transsarcolemmal Ca permeation is slow, DCa is the diffusion coefficient in the extracellular region. The paired ratios DCa/Ds averaged 1.32 +/- 0.05 (n = 67) for all levels of Cao but at physiologic or higher Cao averaged 1.45 +/- 0.07 (n = 39), close to the ratio of free diffusion coefficients, 1.53. Equations distinguishing transient from steady state diffusion were fitted to the data, showing that the apparent distribution volume of "binding sites" external to the diffusion pathway diminished at higher Cao in a fashion suggesting that a least two different Ca2+ binding sites were present.

Animals↗

A milling crowd model for local and long-range obstructed lateral diffusion. Mobility of excimeric probes in the membrane of intact erythrocytes.

A new model for lateral diffusion, the milling crowd model (MC), is proposed and is used to derive the dependence of the monomeric and excimeric fluorescence yields of excimeric membrane probes on their concentration. According to the MC model, probes migrate by performing spatial exchanges with a randomly chosen nearest neighbor (lipid or probe). Only nearest neighbor probes, one of which is in the excited state, may form an excimer. The exchange frequency, and hence the local lateral diffusion coefficient, may then be determined from experiment with the aid of computer simulation of the excimer formation kinetics. The same model is also used to study the long-range lateral diffusion coefficient of probes in the presence of obstacles (e.g., membrane proteins). The dependence of the monomeric and excimeric fluorescence yields of 1-pyrene-dodecanoic acid probes on their concentration in the membranes of intact erythrocytes was measured and compared with the prediction of the MC model. The analysis yields an excimer formation rate for nearest neighbor molecules of approximately 1 X 10(7) s-1 and an exchange frequency of approximately greater than 2 X 10(7) s-1, corresponding to a local diffusion coefficient of greater than 3 X 10(-8) cm2 s-1. This value is several times larger than the long-range diffusion coefficient for a similar system measured in fluorescence photobleaching recovery experiments. The difference is explained by the fact that long-range diffusion is obstructed by dispersed membrane proteins and is therefore greatly reduced when compared to free diffusion. The dependence of the diffusion coefficient on the fractional area covered by obstacles and on their size is derived from MC simulations and is compared to those of other theories lateral diffusibility.

Diffusion↗

Lateral diffusion in an archipelago. The effect of mobile obstacles.

Lateral diffusion of mobile proteins and lipids (tracers) in a membrane is hindered by the presence of proteins (obstacles) in the membrane. If the obstacles are immobile, their effect may be described by percolation theory, which states that the long-range diffusion constant of the tracers goes to zero when the area fraction of obstacles is greater than the percolation threshold. If the obstacles are themselves mobile, the diffusion constant of the tracers depends on the area fraction of obstacles and the relative jump rate of tracers and obstacles. This paper presents Monte Carlo calculations of diffusion constants on square and triangular lattices as a function of the concentration of obstacles and the relative jump rate. The diffusion constant for particles of various sizes is also obtained. Calculated values of the concentration-dependent diffusion constant are compared with observed values for gramicidin and bacteriorhodopsin. The effect of the proteins as inert obstacles is significant, but other factors, such as protein-protein interactions and perturbation of lipid viscosity by proteins, are of comparable importance. Potential applications include the diffusion of proteins at high concentrations (such as rhodopsin in rod outer segments), the modulation of diffusion by release of membrane proteins from cytoskeletal attachment, and the diffusion of mobile redox carriers in mitochondria, chloroplasts, and endoplasmic reticulum.

Cell Membrane↗

Antibody diffusion in human cervical mucus.

The mucosal immune system actively transports large quantities of antibodies into all mucus secretions, and these secreted antibodies help prevent infectious entry of many pathogens. Mucus is generally thought to protect epithelial cells by forming a diffusional barrier through which only small molecules can pass. However, electron microscopy indicates that the pore size in mucus is approximately 100 nm, which suggests that antibodies as well as other large molecules might also diffuse through mucus. We measured the diffusion coefficients for antibodies and other proteins within human midcycle cervical mucus using two techniques: fluorescence imaging of concentration profiles and fluorescence photobleaching recovery. The two techniques are complementary, since the rates of diffusion are observed over millimeter distances with fluorescence imaging of concentration profiles and micron distances with fluorescence photobleaching recovery. Both methods yielded essentially the same diffusion coefficients. In contrast to previous reports indicating mucus significantly impedes diffusion of small molecules, antibody diffusion in mucus was relatively unimpeded. In our observations IgG, IgG fragments, IgA, and IgM diffused almost as rapidly in cervical mucus as in water (1.0 > Dmucus/Dwater > 0.7). Simple models for diffusion through water-filled pores suggest that the hydrodynamic pore size for cervical mucus is approximately 100 nm, smaller than the approximately 1000 nm pore size of a collagen gel (at 1 mg/ml) and larger than the approximately 10 nm pore size of gelatin (at 100 mg/ml). This estimated pore size is consistent both with electron micrographs and geometric models of interfiber spacing. Based on these results, we predict that particles as large as viruses can diffuse rapidly through human midcycle cervical mucus, provided the particle forms no adhesive interactions with mucus glycoproteins.

Antibodies↗

Diffusion coefficient of the cyclic GMP analog 8-(fluoresceinyl)thioguanosine 3',5' cyclic monophosphate in the salamander rod outer segment.

Cyclic GMP (cGMP) is the intracellular messenger mediating phototransduction in retinal rods, with its longitudinal diffusion in the rod outer segment (ROS) likely to be a factor in determining light sensitivity. From the kinetics of cGMP-activated currents in the truncated ROS of the salamander (Ambystoma tigrinum), the cGMP diffusion coefficient was previously estimated to be approximately 60 x 10(-8) cm2 s-1. On the other hand, fluorescence measurements in intact salamander ROS using 8-(fluoresceinyl)thioguanosine 3',5'-cyclic monophosphate (Fl-cGMP) led to a diffusion coefficient for this compound of 1 x 10(-8) cm2 s-1; after corrections for differences in size and in binding to cellular components between cGMP and Fl-cGMP, this gave an upper limit of 11 x 10(-8) cm2 s-1 for the cGMP diffusion coefficient. To properly compare the two sets of measurements, we have examined the diffusion of Fl-cGMP in the truncated ROS. From the kinetics of Fl-cGMP-activated currents, we have obtained a diffusion coefficient of 3 x 10(-8) cm2 s-1 for this analog; the cGMP diffusion coefficient measured from the same truncated ROSs was approximately 80 x 10(-8) cm2 s-1. Thus, a factor of 27 appears appropriate for correcting differences in size and intracellular binding between cGMP and Fl-cGMP. Application of this correction factor to the Fl-cGMP diffusion coefficient measurements by Olson and Pugh (1993) gives a cGMP diffusion coefficient of approximately 30 x 10(-8) cm2 s-1, in reasonable agreement with the value measured from the truncated ROS.

Ambystoma↗

Cytoplasmic viscosity near the cell plasma membrane: translational diffusion of a small fluorescent solute measured by total internal reflection-fluorescence photobleaching recovery.

Total internal reflection-fluorescence recovery after photobleaching (TIR-FRAP) was applied to measure solute translational diffusion in the aqueous phase of membrane-adjacent cytoplasm. TIR fluorescence excitation in aqueous solutions and fluorescently labeled cells was produced by laser illumination at a subcritical angle utilizing a quartz prism; microsecond-resolution FRAP was accomplished by acousto-optic modulators and electronic photomultiplier gating. A mathematical model was developed to determine solute diffusion coefficient from the time course of photobleaching recovery, bleach time, bleach intensity, and evanescent field penetration depth; the model included irreversible and reversible photobleaching processes, with triplet state diffusion. The validity and accuracy of TIR-FRAP measurements were first examined in aqueous fluorophore solutions. Diffusion coefficients for fluorescein isothiocyanate-dextrans (10-2000 kDa) determined by TIR-FRAP (recovery t1/2 0.5-2.2 ms) agreed with values measured by conventional spot photobleaching. Model predictions for the dependence of recovery curve shape on solution viscosity, bleach time, and bleach depth were validated experimentally using aqueous fluorescein solutions. To study solute diffusion in cytosol, MDCK epithelial cells were fluorescently labeled with the small solute 2',7'-bis-2-carboxyethyl-5-carboxyfluorescein-acetoxymethyl-ester (BCECF). A reversible photobleaching process (t1/2 approximately 0.5 ms) was identified that involved triplet-state relaxation and could be eliminated by triplet-state quenching with 100% oxygen. TIR-FRAP t1/2 values for irreversible BCECF bleaching, representing BCECF translational diffusion in the evanescent field, were in the range 2.2-4.8 ms (0.2-1 ms bleach times), yielding a BCECF diffusion coefficient 6-10-fold less than that in water. These results establish the theory and the first experimental application of TIR-FRAP to measure aqueous-phase solute diffusion, and indicate slowed translational diffusion of a small solute in membrane-adjacent cytosol.

Animals↗

Anomalous diffusion due to binding: a Monte Carlo study.

In classical diffusion, the mean-square displacement increases linearly with time. But in the presence of obstacles or binding sites, anomalous diffusion may occur, in which the mean-square displacement is proportional to a nonintegral power of time for some or all times. Anomalous diffusion is discussed for various models of binding, including an obstruction/binding model in which immobile membrane proteins are represented by obstacles that bind diffusing particles in nearest-neighbor sites. The classification of binding models is considered, including the distinction between valley and mountain models and the distinction between singular and nonsingular distributions of binding energies. Anomalous diffusion is sensitive to the initial conditions of the measurement. In valley models, diffusion is anomalous if the diffusing particles start at random positions but normal if the particles start at thermal equilibrium positions. Thermal equilibration leads to normal diffusion, or to diffusion as normal as the obstacles allow.

Animals↗