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Biomedical subjects

Anne M Mayes

Publications and source records attributed to Anne M Mayes.

11 recordsLinked to original sources
PubMed2007

Formation of osteogenic colonies on well-defined adhesion peptides by freshly isolated human marrow cells.

Bone graft performance can be enhanced by addition of connective tissue progenitors (CTPs) from fresh bone marrow in a manner that concentrates the CTP cell population within the graft. Here, we used small peptide adhesion ligands presented against an otherwise adhesion-resistant synthetic polymer background in order to illuminate the molecular basis for the attachment and colony formation by osteogenic CTPs from fresh human marrow, and contrast the behavior of fresh marrow to many commonly used osteogenic cell sources. The linear GRGDSPY ligand was as effective as tissue culture polystyrene in fostering attachment of culture-expanded porcine CTPs. Although this GRGDSPY peptide was more effective than control peptides in fostering alkaline phosphatase (AP)-positive colony formation from primary human marrow in 5 of the 7 patients tested, GRGDSPY was as effective as the control glass substrate in only one patient of 7. Thus, the peptide appears capable of enabling osteoblastic development from only a subpopulation of CTPs in marrow. The bone sialoprotein-derived peptide FHRRIKA was ineffective in fostering attachment of primary culture-expanded pig CTPs, although it was as effective as GRGDSPY in fostering AP-positive colonies from fresh human marrow. This study provides insights into integrin-mediated behaviors of CTPs and highlights differences between freshly isolated marrow and culture-expanded cells.

Bone Marrow Cells↗
PubMed2006

Photo-cross-linkable polyelectrolyte multilayers for 2-D and 3-D patterning.

We report the synthesis of poly(acrylic acid-ran-vinylbenzyl acrylate) (PAArVBA), a photo-cross-linkable weak polyelectrolyte, and its incorporation into polyelectrolyte multilayer (PEM) films. PEM films assembled from PAArVBA and poly(allylamine hydrochloride) (PAH) are found to exhibit similar thickness trends with assembly pH as those previously reported for poly(acrylic acid) (PAA)/PAH multilayers. Swelling properties of the as-built and photo-cross-linked films are studied by in situ ellipsometry. Two-dimensional masking techniques are used to pattern regions of high and low swelling, as confirmed by atomic force microscopy (AFM), and to provide spatial control over the low-pH-induced microporosity transition exhibited by PAH/PAA PEMs. Films containing alternating blocks of PAH/PAArVBA bilayers and PAH/PAA bilayers were assembled, laterally photopatterned, and exposed to low-pH solution to generate nanoporosity leading to patterned Bragg reflectors, thereby demonstrating three-dimensional control over film structure in these weak PEM assemblies.

Journal Article↗
PubMed2006

Self-assembled one-dimensional nanostructure arrays.

A range of proposed devices relies on the electronic, optical or magnetic properties of one-dimensional (1D) chains of nanoparticles. Here, well-controlled 1D arrays have been formed by templating a spherical-morphology block copolymer within a narrow groove. Significantly, the domains are distorted into ellipses with aspect ratio and major axis orientation controlled by the groove width. This technique gives unprecedented control over the period, particle size, aspect ratio, and orientation of nanoparticles in 1D arrays, making it valuable for creating self-assembled masks for the fabrication of novel devices.

Computer Simulation↗
PubMed2005

Polysulfone-graft-poly(ethylene glycol) graft copolymers for surface modification of polysulfone membranes.

Amphiphilic graft copolymers having polysulfone (PSf) backbones and poly(ethylene glycol) (PEG) side chains were synthesized via reaction of an alkoxide formed from PEG and a base (sodium hydride) with chloromethylated polysulfone. The resulting polysulfone-graft-poly(ethylene glycol), PSf-g-PEG, materials were hydrophilic but water insoluble, rendering them potentially useful as biomaterial coatings. PSf-g-PEG films exhibited high resistance to protein adsorption and cell attachment. When used as an additive in PSf membranes prepared by immersion precipitation, the graft copolymer preferentially segregates to the membrane surface, delivering enhanced wettability, porosity and protein resistance compared to unmodified PSf membranes. The surface properties of PSf-g-PEG modified membranes render them desirable candidates for hemodialysis.

Animals↗
PubMed2004

Nanostructure engineering by templated self-assembly of block copolymers.

Self-assembling materials are the building blocks for bottom-up nanofabrication processes, but many self-assembled nanostructures contain defects and lack sufficient long-range order for certain nanotechnology applications. Here we investigate the formation of defects in a self-assembled array of spherical block-copolymer microdomains, using topographical templates to control the local self-assembly. Perfect ordered sphere arrays can form in both constant-width templates and width-modulated templates. For modulated templates, transition between configurations having a constant number of rows and configurations of stable arrays with varying numbers of rows is shown to be analogous to dislocation formation in an epitaxial thin film system. Based on the configuration transition energy and fluctuation energy, designed templates with a high tolerance for lithographical imperfections can direct precisely modulated block-copolymer nanostructures. This study provides insights into the design of hybrid systems combining top-down and bottom-up fabrication.

Nanotechnology↗
PubMed2004

Effects of temperature and pH on the helicity of a peptide adsorbed to colloidal silica.

The conformation of a cationic alpha-helical peptide (DDDDAAAARRRRR) adsorbed to anionic colloidal silica has been investigated by circular dichroism (CD) spectroscopy as a function of temperature and pH in order to examine how the structure of an adsorbed molecule responds to two simultaneous perturbations. Increased temperature destabilizes the helicity of the peptide in solution, while pH changes alter the substrate surface charge and the corresponding strength of the interaction with the peptide. Near neutral pH, the helicity of the adsorbed peptide, which is determined from the intensity of the CD signal at 222 nm, decreases with increasing temperature, similarly to the temperature-dependent behavior observed for the peptide in aqueous solution. By contrast, at basic pH and a strongly negative surface charge, the helicity of the adsorbed peptide increases with temperature. In order to elucidate the origin of the reversal of the temperature dependence of helicity, a statistical model for the conformation of the adsorbed peptide has been formulated based on the Lifson-Roig model for the helix-coil transition of the peptide in solution. The model provides insight into the trends in fractional helicity and reveals that the temperature dependence of the helicity of the adsorbed peptide results from a competition between the intramolecular interactions that promote helicity and the intermolecular interactions with the surface. The statistical model also enables estimation of the free energy contributions from specific aspects of the adsorption process. Through identification of a connection between the conformation of adsorbed peptide and the interactions of the peptide with the surface, this work suggests a route for the control of adsorbate conformation through peptide and surface engineering.

Adsorption↗
PubMed2003

Low-temperature processing of 'baroplastics' by pressure-induced flow.

The manufacturing of plastics traditionally involves melt processing at temperatures typically greater than 200 degrees C-to enable extrusion or moulding under pressure into desired forms-followed by solidification. This process consumes energy and can cause substantial degradation of polymers and additives (such as flame retardants and ultraviolet stabilizers), limiting plastics performance and recyclability. It was recently reported that the application of pressure could induce melt-like behaviour in the block copolymer polystyrene-block-poly(n-butyl methacrylate) (PS-b-PBMA), and this behaviour has now been demonstrated in a range of other block copolymer systems. These polymers have been termed baroplastics. However, in each case, the order-to-disorder transition, which gives rise to the accompanying change in rheology from soft solid to melt, was observed at temperatures far exceeding the glass transition temperatures (T(g)) of both components. Here we show that baroplastic systems containing nanophase domains of one high-T(g) and one low-T(g) component can exhibit melt-like flow under pressure at ambient temperature through an apparent semi-solid partial mixing mechanism that substantially preserves the high-T(g) phase. These systems were shredded and remoulded ten times with no evident property degradation. Baroplastics with low-temperature formability promise lower energy consumption in manufacture and processing, reduced use of additives, faster production and improved recyclability, and also provide potential alternatives to current thermoplastic elastomers, rubber-modified plastics, and semi-crystalline polymers.

Journal Article↗
PubMed2002

Polymer--calcium phosphate cement composites for bone substitutes.

The use of self-setting calcium phosphate cements (CPCs) as bioresorbable bone-replacement implant materials presently is limited to non-load-bearing applications because of their low compressive strength relative to natural bone. The present study investigated the possibility of strengthening a commercially available CPC, alpha-BSM, by incorporating various water-soluble polymers into the cement paste during setting. Several polyelectrolytes, poly(ethylene oxide), and the protein bovine serum albumin (BSA) were added in solution to the cement paste to create calcium phosphate-polymer composites. Composites formulated with the polycations poly(ethylenimine) and poly(allylamine hydrochloride) exhibited compressive strengths up to six times greater than that of pure alpha-BSM material, with a maximum value reached at intermediate polymer content and for the highest molecular weight studied. Composites containing BSA developed compressive strengths twice that of the original cement at protein concentrations of 13-25% by weight. In each case, XRD studies correlate the improvement in compressive strength with reduced crystallite dimensions, as evidenced by a broadening of the (0,0,2) reflection. This suggests that polycation or BSA adsorption inhibits crystal growth and possibly leads to a larger crystal aspect ratio. SEM results indicate a denser, more interdigitated microstructure. The increased strength was attributed to the polymer's capacity to bridge between multiple crystallites (thus forming a more cohesive composite) and to absorb energy through plastic flow.

Animals↗
PubMed2002

Co-regulation of cell adhesion by nanoscale RGD organization and mechanical stimulus.

Integrin-mediated cell adhesion is central to cell survival, differentiation and motility. Many cell responses induced by integrins require both receptor occupancy and receptor aggregation, and appear to be regulated by both biochemical and biophysical means. Multidomain extracellular matrix molecules may serve to foster integrin aggregation by presenting local clusters of adhesion ligands, a hypothesis supported by studies with synthetic substrates showing that cell adhesion and migration are enhanced when adhesion ligands are presented in nanoscale clusters. Here, we used a novel synthetic polymer system to present the adhesion ligand GRGDSPK in nanoscale clusters with 1.7, 3.6 or 5.4 peptides per cluster against a non-adhesive background, where the peptide is mobile on a 2 nm polyethylene oxide tether. Average ligand density ranged from 190 to 5270 RGD/microm(2). We used these substrates to study the effects of ligand density and clustering on adhesion of wild-type NR6 fibroblasts, which express alphavbeta3 and alpha5beta1, integrins known to bind to linear RGD peptides. The strength of cell-substratum adhesion was quantified using a centrifugal detachment assay to assess the relative number of cells remaining adherent after a 10 minute application of defined distraction force. An unusual relationship between cell detachment and distraction force at relatively low values of applied force was found on substrates presenting the clustered ligand. Although a monotonic decrease in the number of cells remaining attached would be expected with increasing force on all substrates, we instead observed a peak (adhesion reinforcement) in this profile for certain ligand conditions. On substrates presenting clustered ligands, the fraction of cells remaining attached increased as the distraction force was increased to between 70 and 150 pN/cell, then decreased for higher forces. This phenomenon was only observed on substrates presenting higher ligand cluster sizes (n=3.6 or n=5.4) and was more pronounced at higher ligand densities. Adhesion reinforcement was not observed on fibronectin-coated surfaces. These results support previous studies showing that biophysical cues such as ligand spatial arrangement and extracellular matrix rigidity are central to the governance of cell responses to the external environment.

3T3 Cells↗
PubMed2002

Simulations of cell-surface integrin binding to nanoscale-clustered adhesion ligands.

Clustering of ligated integrins strongly influences integrin signaling and mechanical linkages between integrins and intracellular structures. Extracellular spatial organization of integrin ligands in clusters may facilitate clustering of bound integrins and thus potentially regulate cellular responses to a defined average amount of ligand in the extracellular environment. The possible role of such ligand clustering effects in controlling overall receptor occupancy is studied here using a simple mass-action equilibrium model as well as a two-dimensional Monte Carlo lattice description of the cell-substrate interface, where cell surface receptors are free to diffuse in the plane of the interface and interact with the substrate-immobilized ligand. Results from the analytical treatment and simulation data indicate that for a single-state model in which receptor-ligand binding equilibria are not influenced by neighboring complexes, clustering of ligand does not enhance total receptor binding. However, if receptor binding energy increases in the presence of neighboring ligated receptors, strong ligand spatial distribution effects arise. Nonlinear responses to increasing ligand density are also observed even in the case of random ligand placement due to stochastic juxtaposition of ligand molecules. These results describe how spatial distribution of ligand presented by the extracellular matrix or by synthetic biomimetic materials might control cell responses to external ligands, and suggest a feedback mechanism by which focal contact formation might be initiated.

Animals↗