Barrier properties of mucus

Cone, Richard A.

doi:10.1016/j.addr.2008.09.008

Cited by 1,219 publications

(1,075 citation statements)

References 89 publications

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“…However, they run contrary to reports that the mucus layer forms a contiguous viscoelastic 'blanket' [41] (figure 7a) that overlies the absorptive surface of epithelial cells and restricts the rate at which nutrients are absorbed. The latter hypothesis is to some extent founded on the properties of mucins that have been 'purified' to remove cellular and other debris [15,27], and hence, may not reflect the heterogeneity that exists in vivo.…”

Section: Discussioncontrasting

confidence: 86%

“…Given that NP microbeads have been found to adhere strongly to mucus [28,29,41], our results suggest either that masses of mucin secreted by individual mucosal goblet cells do not always 'anneal' to neighbours [45] to form a contiguous layer, or that sites of translational diffusion and reptative inter-digitation of adjacent mucin masses are more vulnerable to digestion by enteral micro-flora. It is known that small variations in the structure of constituent mucin polymer chains can disrupt their configuration, obstructing reptative diffusion and impeding annealing [45].…”

Section: Discussionmentioning

confidence: 87%

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An exploration of the microrheological environment around the distal ileal villi and proximal colonic mucosa of the possum ( Trichosurus vulpecula )

Lim

Williams

Lentle

et al. 2013

J. R. Soc. Interface.

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Multiple particle-tracking techniques were used to quantify the thermally driven motion of ensembles of naked polystyrene (0.5 mm diameter) microbeads in order to determine the microrheological characteristics around the gut mucosa. The microbeads were introduced into living ex vivo preparations of the wall of the terminal ileum and proximal colon of the brushtail possum (Trichosurus vulpecula). The fluid environment surrounding both the ileal villi and colonic mucosa was heterogeneous; probably comprising discrete viscoelastic regions suspended in a continuous Newtonian fluid of viscosity close to water. Neither the viscosity of the continuous phase, the elastic modulus (G') nor the sizes of viscoelastic regions varied significantly between areas within 20 mm and areas more than 20 mm from the villous mucosa nor from the tip to the sides of the villous mucosa. The viscosity of the continuous phase at distances further than 20 mm from the colonic mucosa was greater than that at the same distance from the ileal villous mucosa. Furthermore, the estimated sizes of viscoelastic regions were significantly greater in the colon than in the ileum. These findings validate the sensitivity of the method and call into question previous hypotheses that a contiguous layer of mucus envelops all intestinal mucosa and restricts diffusive mass transfer. Our findings suggest that, in the terminal ileum and colon at least, mixing and mass transfer are governed by more complex dynamics than were previously assumed, perhaps with gel filtration by viscoelastic regions that are suspended in a Newtonian fluid.

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Section: Discussioncontrasting

confidence: 86%

Section: Discussionmentioning

confidence: 87%

An exploration of the microrheological environment around the distal ileal villi and proximal colonic mucosa of the possum ( Trichosurus vulpecula )

Lim

Williams

Lentle

et al. 2013

J. R. Soc. Interface.

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“…The mucus consists of a physically crosslinked, viscoelastic hydrogel, with mesh sizes of the order of 10-100 nm (ref. 40). Barrier penetration is largely restricted for particles that are greater in diameter than a few hundred nanometres 40,41 , although particles that are ~50 nm in diameter can diffuse in mucus almost as freely as they do in water 40 .…”

Section: Materials For Penetrating Mucosal Barriersmentioning

confidence: 99%

Materials engineering for immunomodulation

Hubbell

Thomas

Swartz

2009

Nature

513

428

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The engineering of materials that can modulate the immune system is an emerging field that is developing alongside immunology. For therapeutic ends such as vaccine development, materials are now being engineered to deliver antigens through specific intracellular pathways, allowing better control of the way in which antigens are presented to one of the key types of immune cell, T cells. Materials are also being designed as adjuvants, to mimic specific 'danger' signals in order to manipulate the resultant cytokine environment, which influences how antigens are interpreted by T cells. In addition to offering the potential for medical advances, immunomodulatory materials can form well-defined model systems, helping to provide new insight into basic immunobiology.The term 'immunobioengineering' is used to describe efforts by immunologists and engineers to design materials, delivery vehicles and molecules both to manipulate and to better understand the immune system. Examples are the engineering of material surfaces to induce or prevent complement activation, the engineering of adjuvants to activate the immune system, the engineering of antigen or adjuvant carriers for subunit vaccine delivery, and the engineering of microenvironments to determine the interaction kinetics of mature dendritic cells and naive T cells. These advances not only will contribute to prophylactic vaccine strategies for infectious diseases but also are likely to affect immunotherapeutics, particularly for cancer, and new approaches to prevent or treat allergies and autoimmune diseases. The field is rapidly evolving along with advances in our understanding of immunology and is also contributing to our knowledge of basic immunology.In this Review, we describe the current state of immunobioengineering as it intersects with the field of materials science, and we give a perspective on its current and future directions. We focus on materials for immunomodulation, particularly with respect to dendritic-cell modulation. We begin by providing a brief introduction to the targets for delivery: the types of cell that materials are being designed to target, the tissues in which those cells reside, the intracellular compartments within those cells, and the influence that delivery to those particular compartments has on immunological outcome. We then discuss the biomolecular payloads used to activate immune cells and the design of the materials used to deliver those 'danger' signals along with, in the context of vaccination, antigens. Finally, we highlight materials approaches that are being developed to explore basic immunological function, especially how dendritic cells and T cells interact. Tissue and cellular targetsAs the general goals of immunobioengineering are to probe and manipulate the immune system, we start with a general discussion of tissue, cellular and subcellular targets -what we want to target and why -to guide the design principles discussed below.The immune cells most frequently targeted include B cells, macrophages and dendritic cells, wh...

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“…Unlike particle diffusion in water, which is non-restrictive and unchangeable with time, particles will undergo varying degrees of hindrance during their diffusion through a polymeric gel matrix such as mucus. Here the mucin fibres are undergoing continuous association and disassociation and the network as a whole undergoes elastic behavior resulting in the formation and collapse of aqueous cages surrounded by mucin fibres [51]. As such there will be significant potential for particle-gel interactions within mucus the probability of which increases as a function of time [52].…”

Section: Multiple Particle Trackingmentioning

confidence: 99%