Biomedical subjects

Iseult Lynch

Publications and source records attributed to Iseult Lynch.

9 recordsLinked to original sources

PubMed2006

Chemical shift imaging of molecular transport in colloidal systems: visualization and quantification of diffusion processes.

Magnetic resonance imaging with chemical shift resolution is demonstrated to provide detailed information about molecular transport on the macroscopic scale in complex colloidal systems. The concentrations of species with distinct 1H resonance lines can be quantified from spatially resolved, high-resolution, 1H nuclear magnetic resonance spectra. The method is demonstrated by experiments on three systems with multiple simultaneous transport processes where the diffusion coefficients depend on position and/or on the concentration of other species: (1) release of poly(ethylene glycol) and imidazole from a hydrogel into an external reservoir of water, (2) migration of acetic acid and tetramethylammonium ions in a highly concentrated water-in-oil emulsion with initially non-uniform concentration of solutes, and (3) release of tetramethylammonium ions loaded into a hydrogel triggered by the diffusion of methyl green into the gel matrix.

Colloids↗

PubMed2006

Molecular basis of cell-biomaterial interaction: insights gained from transcriptomic and proteomic studies.

With the growing interest in clinical interventions that involve medical devices, the role for new biomaterials in modern medicine is currently expanding at a phenomenal rate. Failure of most implant materials stems from an inability to predict and control biological phenomena, such as protein adsorption and cell interaction, resulting in an inappropriate host response to the materials. Contemporary advances in biological investigation are starting to shift focus in the biomaterials field, in particular with the advent of high-throughput methodologies for gene and protein expression profiling. Here, we examine the role that emerging transcriptomic and proteomic technologies could play in relation to biomaterial development and usage. Moreover, a number of studies are highlighted which have utilized such approaches in order to try to create a deeper understanding of cell-biomaterial interactions and, hence, improve our ability to predict and control the biocompatibility of new materials.

Biocompatible Materials↗

PubMed2006

Novel method to prepare morphologically rich polymeric surfaces for biomedical applications via phase separation and arrest of microgel particles.

We outline here a simple method to prepare polymeric surfaces of controlled surface topography on the micrometer scale, via assembly and arrest of microgel particles, for use in a range of biological applications to modify cell adhesion and spreading. In previous work by other groups, it has transpired that topography on the nanoscale is unlikely to be useful for this purpose, as roughness on this scale is often covered or coated by serum derived proteins during the early stages of cell adhesion and cells can easily bridge nanoscale roughness. Therefore, in our work, we have focused on roughness or topographic variations on the micrometer length scale. The basic idea is to modify the interactions between particles, thereby causing the microgel particles to phase separate into particle-dense and particle-dilute domains and to arrest these domains on the surface. The result is the creation of surfaces with controlled topography. By changing the particle size, it is possible to alter the size of the pores formed and their distribution in the film. Preliminary results show that the system can readily be arrested into a homologous series of such structures (formed from microgel particles of the same size and same chemical structure) with biological implications. At the extremes of this series, large phenotypic differences are observed between cells, ranging (at one end) from localization of the cells in the pores to (at the other end) cells that avoid such localization, and remain extended, growing along the ridges between the pores. This constitutes a sort of cell localization transition on a surface with identical chemical components, where only the morphology has been adjusted.

Acrylamides↗

PubMed2006

Detecting cryptic epitopes created by nanoparticles.

As potential applications of nanotechnology and nanoparticles increase, so too does the likelihood of human exposure to nanoparticles. Because of their small size, nanoparticles are easily taken up into cells (by receptor-mediated endocytosis), whereupon they have essentially free access to all cellular compartments. Similarly to macroscopic biomaterial surfaces (that is, implants), nanoparticles become coated with a layer of adsorbed proteins immediately upon contact with physiological solutions (unless special efforts are taken to prevent this). The process of adsorption often results in conformational changes of the adsorbed protein, which may be affected by the larger curvature of nanoparticles compared with implant surfaces. Protein adsorption may result in the exposure at the surface of amino acid residues that are normally buried in the core of the native protein, which are recognized by the cells as "cryptic epitopes." These cryptic epitopes may trigger inappropriate cellular signaling events (as opposed to being rejected by the cells as foreign bodies). However, identification of such surface-exposed epitopes is nontrivial, and the molecular nature of the adsorbed proteins should be investigated using biological and physical science methods in parallel with systems biology studies of the induced alterations in cell signaling.

Adsorption↗

PubMed2006

Surface-induced changes in protein adsorption and implications for cellular phenotypic responses to surface interaction.

Understanding external factors that determine cellular phenotypic responses is of key interest in the field of biomaterials. Currently, material surface characteristics, protein adsorption and cellular phenotypic responses are all considered to be interrelated and ultimately determine the biocompatibility of materials. The exact nature of the relationship between these distinct, yet related, phenomena still remains to be elucidated. Through the use of a series of thermoresponsive N-isopropylacrylamide-based co-polymer films, we aimed to shed light on the relationship between surface hydrophobicity, protein adsorption and subsequent cellular response. Despite changes in co-polymer hydrophobicity mediated by altered ratios of constituent monomers, differential cellular response was only apparent in the presence of serum. Co-polymer films displayed alterations with respect to the amount of protein adsorbed on the surface, with individual serum proteins (albumin and fibronectin) displaying contrasting adsorption characteristics. Changes in protein adsorption corresponded to changes in cell adhesion, cytoskeletal organisation and cell morphology, as well as to changes in cell movement and intracellular signalling events. Examination of focal adhesion kinase (FAK), and extracellular signal-regulated kinase (ERK 1/2), important mediators of adhesion and growth factor-related signalling events, revealed a comparative reduction in phosphorylation of these signalling proteins in cells grown on co-polymers in comparison to those cultured on tissue culture polystyrene (TCP; used as a control surface). We also associated surface-mediated phenotypic alterations of cells grown on TCP and co-polymer films with particular changes in gene expression. These results indicate that cellular response to interaction with our series of co-polymer films is determined by the surface-adsorbed protein layer, which in turn is determined by the changing surface chemistry as the ratio of the co-monomers is altered.

Acrylamides↗

PubMed2006

Presence or absence of counterion specificity in the interaction of alkylammonium surfactants with alkylacrylamide gels.

Patterns in the interaction of cationic surfactants with nonionic polymer gels, which were inferred from a recent study from our laboratory, are confirmed by measurements of a series of alkylammonium surfactants with different counterions with a series of alkyl acrylamide gels of increasing hydrophobicity. Two swelling patterns were observed: Either the swelling continued above the surfactant critical micelle concentration (cmc) and the maximum swelling differed for different counterions and increased in the order of Br-<Cl-<Ac-, in agreement with the degree of dissociation of these counterions and with the Hofmeister series or the swelling stopped below (or close to) the surfactant cmc, implying saturation binding, and the maximum swelling was similar for each of the three counterions. Binding studies confirmed that the amount of surfactant bound depends on the counterion in cases where saturation binding is not reached but not in cases where saturation binding is reached. The swelling/binding patterns could be rationalized in terms of a shift from partial binding to saturation binding with increasing gel hydrophobicity and an electrostatic intermicellar repulsion effectively independent of specific counterion binding, owing to "condensation" at the highly charged micellar surface.

Acrylamide↗

PubMed2005

Simultaneous release of hydrophobic and cationic solutes from thin-film "plum-pudding" gels: a multifunctional platform for surface drug delivery?

The release of two compositionally different solutes from a composite gel composed of two different populations of microgel particles embedded in a single bulk gel matrix is described, showing the potential of the "plum-pudding gel" as a multifunctional platform for controlled surface release. One hydrophobic solute (pyrene) and one hydrophobic and charged solute (rhodamine 123) were chosen as the solutes to be released. Hydrophobic microgels composed of 50% N-isopropylacrylamide (NIPAM) and 50% N-tert-butylacrylamide (BAM) were loaded with pyrene, and anionic microgels composed of 30% acrylic acid (AAc), 20% NIPAM, and 50% BAM were loaded with rhodamine 123. The two solute-loaded microgel populations were incorporated into a single bulk gel network, from which the two solutes were released simultaneously and independently. Using this structural motif, solutes that are mutually incompatible can be incorporated into a single matrix with which they may also be incompatible. The electrostatically incorporated solute was released much more slowly than the hydrophobically attracted solute, indicating that the microgel composition can be tailored to the specific solute, and thus control its release rate. The choice of bulk matrix was also found to influence the release rate much more than expected, offering a further control element to the system.

Drug Delivery Systems↗

PubMed2005

Reswelling of polyelectrolyte hydrogels by oppositely charged surfactants.

The interactions between charged alkylacrylamide gels of varying hydrophobicity and charge density and the oppositely charged surfactant hexadecyltrimethylammonium (C16TA+) have been investigated to determine the conditions necessary to induce excess surfactant binding (beyond charge neutralization) and resolubilization of the polymer-surfactant complex. In all cases, an initial gel collapse occurred due to neutralization of the charges in the gel, and the volume of the collapsed gel was smaller than that of the corresponding neutral gel at the same surfactant concentration, as a result of the formation of interchain micellar cross-links. For gels containing neutral repeating units that were found previously to bind C16TA+, a subsequent sharp reswelling of the gel network occurred, beginning at a critical surfactant concentration called the cac(2). The reswelling is due to binding of excess surfactant, which results in the gels becoming recharged. For gels whose neutral repeating units do not bind C16TA+, there was no reswelling behavior (no cac(2)), but there was a gradual increase of the swelling back to that of the equivalent neutral gel with increasing surfactant concentration. The results are interpreted in terms of the expected surfactant binding isotherm.

Journal Article↗

PubMed2005

Hydrophobicity and counterion effects on the binding of ionic surfactants to uncharged polymeric hydrogels.

Gel swelling experiments have been used to study the binding of ionic surfactants to a series of nonionic alkylacrylamide hydrogels of increasing hydrophobicity. The binding of hexadecyl trimethylammonium (C16TA+) to uncharged gels is sensitive to both the hydrophobicity of the gel and the counterion to the surfactant. There is a minimum hydrophobicity threshold below which binding of the surfactant does not occur, and this is influenced by the counterion to the surfactant. The surfactant concentration at the onset of binding, the critical association concentration (cac), decreases with increasing gel hydrophobicity. The maximum swelling of the gel (at intermediate network hydrophobicity) increases in the order of the Hofmeister series of anions, bromide (Br-) < chloride (Cl-) < acetate (Ac-). At higher gel hydrophobicity, differences in swelling are no longer observed on changing the counterion. A minimum hydrophobicity threshold was also found for the binding of the anionic surfactants sodium dodecyl sulfate (SDS) and sodium dodecyl-di(ethylene oxide)-sulfate (SD-(EO)2-S). Differences in the swelling behavior with network hydrophobicity are explained in terms of the degree of saturation of the gel with surfactant at the cmc.

Journal Article↗