Biomedical subjects

David M Collard

Publications and source records attributed to David M Collard.

9 recordsLinked to original sources

PubMed2006

Stacked conjugated oligomers as molecular models to examine interchain interactions in conjugated materials.

Previous studies of the redox states of linear conjugated oligomers as models for polarons and bipolarons in conjugated polymers do not fully address the influence of intermolecular interactions on the electronic structure of conjugated systems in the solid state. Fusion of oligothiophenes onto a bicyclo[4.4.1]undecane core holds the conjugated oligomers in a permanent cofacial stack. One- and two-electron oxidation of the stacked oligomers affords mono(radical cation)s and dications that serve as models for polarons and bipolarons in p-doped conjugated polymers and demonstrates the effect of pi-stacking on the electronic structure of these species.

Journal Article↗

PubMed2006

Switchable gratings by spatially periodic alignment of liquid crystals via patterned photopolymerization.

Spatially periodic patterning of the anchoring condition of a nematic liquid crystal (NLC) within a polymer matrix via a patterned photopolymerization affords a novel and facile method to prepare electrically switchable diffraction gratings. UV irradiation through a photomask of two comonomers, with opposite tendencies to align the NLC and also with different reactivity ratios, leads to definition of areas with either homeotropic or planar alignment of the NLC. Photopolymerization-induced diffusion of the monomers accounts for the spatial distribution of the concentration of these monomers. The resulting diffraction gratings are switchable under low electric fields and possess structural stability offered by the polymer matrix.

Journal Article↗

PubMed2006

Functional lactide monomers: methodology and polymerization.

Side-chain-functionalized lactide analogues have been synthesized from commercially available amino acids and polymerized using stannous octoate as a catalyst. The synthetic strategy presented allows for the incorporation of any protected amino acid for the preparation of functionalized diastereomerically pure lactide monomers. The resulting functionalized cyclic monomers can be homopolymerized and copolymerized with lactides and then quantitatively deprotected forming new functional poly(lactide)-based materials. This strategy allows for the introduction of functional groups along a poly(lactide) (PLA) backbone that after deprotection can be viewed as chemical handles for further functionalization of PLA, yielding improved biomaterials for a variety of applications.

Amino Acids↗

PubMed2005

Control of anchoring of nematic fluids at polymer surfaces created by in situ photopolymerization.

In situ photopolymerization of alkyl acrylate monomers in the presence of a nematic fluid provides a cellular matrix of liquid crystalline droplets in which the chemical structure of the encapsulating polymer exerts control over the alignment (anchoring) of the liquid crystalline molecules. Control is obtained by variation of the alkyl side chains and through copolymerization of two dissimilar monofunctional acrylates. For example, among a series of poly(methylheptyl acrylate)s, the 1-methylheptyl analogue prefers planar anchoring of a nematic (TL205) over the temperature range studied. However, the polymers of other methylheptyl side chains display a homeotropic-to-planar anchoring thermal transition temperature similar to that of the n-heptyl analogue. Copolymerization of two monofunctional acrylates with opposing tendencies of aligning liquid crystal leads to tunability of anchoring behavior over a wide temperature range. The broad anchoring transitions we observed provide a way of achieving highly tilted anchoring.

Journal Article↗

PubMed2005

Integrin binding specificity regulates biomaterial surface chemistry effects on cell differentiation.

Biomaterial surface chemistry has profound consequences on cellular and host responses, but the underlying molecular mechanisms remain poorly understood. Using self-assembled monolayers as model biomaterial surfaces presenting well defined chemistries, we demonstrate that surface chemistry modulates osteoblastic differentiation and matrix mineralization independently from alterations in cell proliferation. Surfaces were precoated with equal densities of fibronectin (FN), and surface chemistry modulated FN structure to alter integrin adhesion receptor binding. OH- and NH(2)-terminated surfaces up-regulated osteoblast-specific gene expression, alkaline phosphatase enzymatic activity, and matrix mineralization compared with surfaces presenting COOH and CH(3) groups. These surface chemistry-dependent differences in cell differentiation were controlled by binding of specific integrins to adsorbed FN. Function-perturbing antibodies against the central cell binding domain of FN completely inhibited matrix mineralization. Furthermore, blocking antibodies against beta(1) integrin inhibited matrix mineralization on the OH and NH(2) surfaces, whereas function-perturbing antibodies specific for beta(3) integrin increased mineralization on the COOH substrate. These results establish surface-dependent differences in integrin binding as a mechanism regulating differential cellular responses to biomaterial surfaces. This mechanism could be exploited to engineer materials that control integrin binding specificity to elicit desired cellular activities to enhance the integration of biomaterials and improve the performance of biotechnological culture supports.

3T3 Cells↗

PubMed2004

Surface chemistry modulates focal adhesion composition and signaling through changes in integrin binding.

Biomaterial surface properties influence protein adsorption and elicit diverse cellular responses in biomedical and biotechnological applications. However, the molecular mechanisms directing cellular activities remain poorly understood. Using a model system with well-defined chemistries (CH3, OH, COOH, NH2) and a fixed density of the single adhesive ligand fibronectin, we investigated the effects of surface chemistry on focal adhesion assembly and signaling. Surface chemistry strongly modulated integrin binding and specificity--alpha5beta1 integrin binding affinity followed the pattern OH>NH2=COOH>CH3, while integrin alphaVbeta3 displayed the relationship COOH>NH2>>OH=CH3. Immunostaining and biochemical analyses revealed that surface chemistry modulates the structure and molecular composition of cell-matrix adhesions as well as focal adhesion kinase (FAK) signaling. The neutral hydrophilic OH functionality supported the highest levels of recruitment of talin, alpha-actinin, paxillin, and tyrosine-phosphorylated proteins to adhesive structures. The positively charged NH2 and negatively charged COOH surfaces exhibited intermediate levels of recruitment of focal adhesion components, while the hydrophobic CH3 substrate displayed the lowest levels. These patterns in focal adhesion assembly correlated well with integrin alpha5beta1 binding. Phosphorylation of specific tyrosine residues in FAK also showed differential sensitivity to surface chemistry. Finally, surface chemistry-dependent differences in adhesive interactions modulated osteoblastic differentiation. These differences in focal adhesion assembly and signaling provide a potential mechanism for the diverse cellular responses elicited by different material properties.

3T3 Cells↗

PubMed2003

Surface chemistry modulates fibronectin conformation and directs integrin binding and specificity to control cell adhesion.

Integrin-mediated cell adhesion to proteins adsorbed onto synthetic surfaces anchors cells and triggers signals that direct cell function. In the case of fibronectin (Fn), adsorption onto substrates of varying properties alters its conformation/structure and its ability to support cell adhesion. In the present study, self-assembled monolayers (SAMs) of alkanethiols on gold were used as model surfaces to investigate the effects of surface chemistry on Fn adsorption, integrin binding, and cell adhesion. SAMs presenting terminal CH(3), OH, COOH, and NH(2) functionalities modulated adsorbed Fn conformation as determined through differences in the binding affinities of monoclonal antibodies raised against the central cell-binding domain (OH > COOH = NH(2) > CH(3)). Binding of alpha(5)beta(1) integrin to adsorbed Fn was controlled by SAM surface chemistry in a manner consistent with antibody binding (OH > COOH = NH(2) > CH(3)), whereas alpha(V) integrin binding followed the trend: COOH >> OH = NH(2) = CH(3), demonstrating alpha(5)beta(1) integrin specificity for Fn adsorbed onto the NH(2) and OH SAMs. Cell adhesion strength to Fn-coated SAMs correlated with alpha(5)beta(1) integrin binding (OH > COOH = NH(2) > CH(3)), and experiments with function-perturbing antibodies demonstrated that this receptor provides the dominant adhesion mechanism in this cell model. This work establishes an experimental framework to analyze adhesive mechanisms controlling cell-surface interactions and provides a general strategy of surface-directed control of adsorbed protein activity to manipulate cell function in biomaterial and biotechnological applications.

Animals↗

PubMed2002

Influence of pi-stacking on the redox properties of oligothiophenes: (alpha-alkyloligo-thienyl)para[2.2]cyclophanes.

[structure: see text] Oligothienyl-substituted paracyclophanes bearing alpha-thienyl substituents, which block polymerization at these sites, undergo oxidation to form stable radical cations and dications. Splitting of the first voltammetric oxidation wave of stacked dimers into two single-electron processes corresponding to formation of the stacked mono(radical cation) and the stacked bis(radical cation) illustrates the influence of pi-stacking on the behavior of conjugated chains, which serve as models for stacked polarons in conjugated polymers.

Journal Article↗

PubMed2002

Control of the anchoring behavior of polymer-dispersed liquid crystals: effect of branching in the side chains of polyacrylates.

A temperature-driven anchoring transition in a polymer/nematic fluid composite that is far from the bulk nematic-isotropic transition temperature is reported. A series of poly(methylheptyl acrylates) were studied to probe the subtle effects of the side chain structure of the polymer on control of the anchoring. A polymer-dispersed liquid crystal film made from TL205 and 1-methylheptyl acrylate shows only planar anchoring over the temperature range studied, while the films made from TL205 and each of the other methylheptyl acrylates or n-heptyl acrylate show the homeotropic-to-planar anchoring transition at temperatures between 70 and 78 degrees C. An interfacial model is proposed in which the different conformation of the side chains is suggested as the cause for the dramatic difference in the observed anchoring behavior.

Journal Article↗