Hindered diffusion in agarose gels: test of effective medium model

Johnson, Erin M.; Berk, David A.; Jain, Rakesh K.; Deen, William M.

doi:10.1016/s0006-3495(96)79645-5

Cited by 302 publications

(339 citation statements)

References 27 publications

(40 reference statements)

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“…Co-infusion of heparin with certain growth factors in vivo also increases their volume of distribution in rat CNS (Hamilton et al 2001). All the molecules in Table 2 (Johnson et al 1995, Johnson et al 1996Stroh et al 2003), fluorescence imaging of profiles (Saltzman et al 1994), and IOI (Tao and Nicholson 1996; this study). OG514-EGF D (20°C) ϭ 11.7 Ϯ 0.18 ϫ 10 Ϫ7 cm 2 /s (n ϭ 8).…”

Section: Egf Diffusion In Brain Is Characterized By Lowmentioning

confidence: 82%

Diffusion of Epidermal Growth Factor in Rat Brain Extracellular Space Measured by Integrative Optical Imaging

Thorne

Hrabětová

Nicholson

2004

Journal of Neurophysiology

152

132

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Diffusion of epidermal growth factor in rat brain extracellular space measured by integrative optical imaging. J Neurophysiol 92: 3471-3481, 2004. First published July 21, 2004 doi:10.1152/jn. 00352.2004. Epidermal growth factor (EGF) stimulates proliferation, process outgrowth, and survival in the CNS. Understanding the actions of EGF necessitates characterizing its distribution in brain tissue following drug delivery or release from cellular sources. We used the integrative optical imaging (IOI) method to measure diffusion of fluorescently labeled EGF (6,600 M r ; 4 g/ml) in the presence of excess unlabeled EGF (90 g/ml) to compete off specific receptor binding and reveal the "true" EGF diffusion coefficient following injection in rat brain slices (400 m). The effective diffusion coefficient was 5.18 Ϯ 0.16 ϫ 10 Ϫ7 (SE) cm 2 /s (n ϭ 22) in rat somatosensory cortex and the free diffusion coefficient, determined in dilute agarose gel, was 16.6 Ϯ 0.12 ϫ 10 Ϫ7 cm 2 /s (n ϭ 27). Tortuosity ( ), a parameter representing the hindrance imposed on EGF by the convoluted brain extracellular space (ECS), was 1.8, the lowest yet measured by IOI for a protein in brain. Control experiments with fluorescent dextran of similar molecular weight and tetramethylammonium confirmed EGF did not affect local ECS structure. We conclude that transport of smaller growth factors such as EGF through brain ECS is less hindered than that of larger proteins (Ͼ10,000 M r , e.g., nerve growth factor) where typically Ͼ 2.1. Modeling was used to predict that low will allow EGF sources in the brain to be further from target cells and still elicit a biological response. High values for larger growth factors imply more constrained local biological effects than with smaller proteins such as EGF.

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Section: Egf Diffusion In Brain Is Characterized By Lowmentioning

confidence: 82%

Diffusion of Epidermal Growth Factor in Rat Brain Extracellular Space Measured by Integrative Optical Imaging

Thorne

Hrabětová

Nicholson

2004

Journal of Neurophysiology

152

132

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“…Using the under-agarose assay, in which cell motion is restricted and the diffusion of large molecules, such as PdsA, is slowed (Johnson et al, 1996), the pdsA Ϫ /PEC cells migrated in a disordered manner, showing broad twisted streams as opposed to the single-file head-to-tail arrays observed in WT cells. In the needle assay, the external cAMP signal diffuses from a point source forming a radial gradient convergent at the needle.…”

Section: Discussionmentioning

confidence: 99%

The Group Migration of Dictyostelium Cells Is Regulated by Extracellular Chemoattractant Degradation

Garcia

Rericha

Heger

et al. 2009

MBoC

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Starvation of Dictyostelium induces a developmental program in which cells form an aggregate that eventually differentiates into a multicellular structure. The aggregate formation is mediated by directional migration of individual cells that quickly transition to group migration in which cells align in a head-to-tail manner to form streams. Cyclic AMP acts as a chemoattractant and its production, secretion, and degradation are highly regulated. A key protein is the extracellular phosphodiesterase PdsA. In this study we examine the role and localization of PdsA during chemotaxis and streaming. We find that pdsA ؊ cells respond chemotactically to a narrower range of chemoattractant concentrations compared with wild-type (WT) cells. Moreover, unlike WT cells, pdsA ؊ cells do not form streams at low cell densities and form unusual thick and transient streams at high cell densities. We find that the intracellular pool of PdsA is localized to the endoplasmic reticulum, which may provide a compartment for storage and secretion of PdsA. Because we find that cAMP synthesis is normal in cells lacking PdsA, we conclude that signal degradation regulates the external cAMP gradient field generation and that the group migration behavior of these cells is compromised even though their signaling machinery is intact. INTRODUCTIONThe process by which cells sense an attractant molecule and respond by migrating directionally toward it is called chemotaxis. Chemotaxis is essential for a variety of physiological processes in mammals as well as for the survival of lower eukaryotes. The mechanisms that regulate the directed migration of neutrophils and Dictyostelium discoideum have been extensively studied previously (van Haastert and Devreotes, 2004;Bagorda et al., 2006;Friedl and Weigelin, 2008;Stephens et al., 2008). One particular challenge of these fast-moving cells is to maintain the ability to respond sensitively and rapidly to an attractant signal. Because both neutrophils and Dictyostelium cells use signal relay loops to propagate chemoattractant signals, mechanisms must be at play to maintain detectable levels of chemoattractants. Remarkably, signal degradation also seems to play an important role in the developmental processes of multicellular organisms. Migration of primordial germ cells in Drosophila and Zebrafish seems to require degradation of specific lysophospholipids in the former or chemokines in the latter to allow these cells to find their proper developmental environment (Renault and Lehmann, 2006;Minina et al., 2007). Many cell types use receptor-mediated degradation to maintain detectable levels of chemoattractants. In this context, cells internalize the bound receptor and as part of the receptor recycling pathway the ligand is released for degradation (Minina et al., 2007;Boldajipour et al., 2008;Borroni et al., 2008;Scola et al., 2008). Alternatively, extracellular enzymes can specifically degrade the extracellular signaling molecules, allowing the sensing machinery to go back to basal levels and retain high se...

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“…Solute behavior in hydrogels has been explained in terms of reduction in hydrogel free volume [20,21,22], enhanced hydrodynamic drag on the solute [23,24], increased path length due to obstruction [25,26], and a combination of hydrodynamic drag and obstruction effects [27].…”

Section: Amsden's Obstruction Scaling Theorymentioning

confidence: 99%

Effect of Cross-Linking on the Diffusion of Water, Ions, and Small Molecules in Hydrogels

2009

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Understanding the diffusion of small molecules in hydrogel system is of major importance in a variety of applications including drug delivery systems, tissue engineering and contact lens. Cross-linking density of hydrogels has been commonly used to tune key parameters like mesh size and molecular weight between cross-linkers, in order to change macroscopic properties of hydrogels. In this thesis, molecular dynamics investigations of chemically-cross-linked poly(ethylene glycol) (PEG) hydrogels are reported with the aim of exploring the diffusion properties of water, ions, and rhodamine within the polymer at the molecular level.The water structure and diffusion properties were studied at various cross-linking densities with molecular weights of the chains ranging from 572 to 3400. As the cross-linking density is increased, the water diffusion decreases and the slowdown in diffusion is more severe at the polymer-water interface. The water diffusion at various cross-linking densities is correlated with the water hydrogen bonding dynamics. The diffusion of ions and rhodamine also decreased as the cross-linking density is increased. The variation of diffusion coefficient with cross-linking density is related to the variation of water content at different cross-linking densities.Comparison of simulation results and obstruction scaling theory for hydrogels showed similar trends.ii To Father and Mother.iii

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Hindered diffusion in agarose gels: test of effective medium model

Cited by 302 publications

References 27 publications

Diffusion of Epidermal Growth Factor in Rat Brain Extracellular Space Measured by Integrative Optical Imaging

Diffusion of Epidermal Growth Factor in Rat Brain Extracellular Space Measured by Integrative Optical Imaging

The Group Migration of Dictyostelium Cells Is Regulated by Extracellular Chemoattractant Degradation

Effect of Cross-Linking on the Diffusion of Water, Ions, and Small Molecules in Hydrogels

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