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Biomedical subjects

Matthew Tirrell

Publications and source records attributed to Matthew Tirrell.

9 recordsLinked to original sources
PubMed2006

Differences between tethered polyelectrolyte chains on bare mica and hydrophobically modified mica.

This study investigates the structures of layers of amphiphilic diblock copolymers of poly(t-butyl styrene)-poly(styrene sulfonate) (PtBS-PSS) adsorbed on both the bare mica surface (hydrophilic) and an octadecyltriethoxysilane (OTE)-modified mica surface (hydrophobic). When the surface is rendered hydrophobic, the nonsoluble block exhibits stronger interaction with the surface and higher adsorbed masses are achieved. Interaction forces between two such adsorbed layers on both substrates were measured using the surface forces apparatus. The effect of salt concentration (Cs) and molecular weight (N) on the height of the self-assembled layers (L0) was examined in each case. The resulting scaling relationship is in good agreement with predictions of the brush model, L0 proportional to N(1.0) in the low-salt limit and L0N(-1) proportional to (Cs/sigma)(-0.32) in the salted regime, when adsorption takes place onto the hydrophobized mica surface. For adsorption on the bare mica surface, L0N(-0.7) proportional, variant Cs(-0.17) agrees with the scaling prediction of the sparse tethering model. The results suggest that, on the hydrophilic bare mica surface, the adsorbed amount is not high enough to form a brush structure and only very little intermolecular stretching of the tethered chains occurs; in contrast, the presence of the hydrophobic OTE layer increases the tethering density such that the polyelectrolyte chains adopt a brush conformation.

Journal Article↗
PubMed2006

Effect of RGD secondary structure and the synergy site PHSRN on cell adhesion, spreading and specific integrin engagement.

The relationship between the form of cell adhesion, ligand presentation, and cell receptor function was characterized using model Langmuir-Blodgett supported films, containing lipid-conjugated peptide ligands, in which isolated variables of the ligand presentation were systematically altered. First, the conformation of an adhesive Arginine-Glycine-Aspartic acid (RGD) peptide was varied by synthesizing linear and looped RGD peptide-containing amphiphiles and subsequently measuring the impact on the function of human umbilical vein endothelial cells. Secondly, the contribution of non-contiguous ligands to cellular engagement was assessed using multi-component biomimetic films. The peptide amphiphiles were composed of fibronectin-derived headgroups--GRGDSP, and its synergy site Pro-His-Ser-Arg-Asn (PHSRN)--attached to hydrocarbon tails. The peptide amphiphiles were diluted using polyethylene glycol (PEG) amphiphiles, where PEG inhibited non-specific cell adhesion. Cells adhered and spread on GRGDSP/PEG systems in a dose-dependent manner. The presentation of GRGDSP influenced integrin cell surface receptor specificity. Results demonstrated that beta1-containing integrins mediated adhesion to the linear GRGDSP presentation to a greater extent than did the alphavbeta3 integrin, and looped GRGDSP preferentially engaged alphavbeta3. GRGDSP/PHSRN/PEG mixtures that closely mimicked the RGD-PHSRN distance in fibronectin, enhanced cell spreading over their two-component analogues. This study demonstrated that controlling the microenvironment of the cell was essential for biomimetics to modulate specific binding and subsequent signaling events.

Amino Acid Sequence↗
PubMed2006

A Monte Carlo simulation study of lipid bilayer formation on hydrophilic substrates from vesicle solutions.

A general lattice Monte Carlo model is used for simulating the formation of supported lipid bilayers (SLBs) from vesicle solutions. The model, based on a previously published paper, consists of adsorption, decomposition, and lateral diffusion steps, and is derived from fundamental physical interactions and mass transport principles. The Monte Carlo simulation results are fit to experimental data at different vesicle bulk concentrations. A sensitivity analysis reveals that the process strongly depends on the bulk concentration C(0), adsorption rate constant K, and all vesicle radii parameters. A measure of "quality of coverage" is proposed. By this measure, the quality of the formed bilayers is found to increase with vesicle bulk concentration.

Adsorption↗
PubMed2005

Self-assembly of model DNA-binding peptide amphiphiles.

Peptide amphiphiles combine the specific functionality of proteins with the engineering convenience of synthetic amphiphiles. These molecules covalently link a peptide headgroup, typically from an active fragment of a larger protein, to a hydrophobic alkyl tail. Our research is aimed at forming and characterizing covalently stabilized, self-assembled, peptide-amphiphile aggregates that can be used as a platform for the examination and modular design and construction of systems with engineering biological activity. We have studied the self-assembly properties of a model DNA-binding amphiphile, having a GCN4 peptide as the headgroup and containing a polymerizable methacrylic group in the tail region, using a combination of small-angle X-ray scattering, small-angle neutron scattering, and cryo- transmission electron microscopy. Our results reveal a variety of morphologies in this system. The peptide amphiphiles assembled in aqueous solution to helical ribbons and tubules. These structures transformed into lamella upon DNA binding. In contrast with common surfactants, the specific interaction between the headgroups seems to play an important role in determining the microstructure. The geometry of the self-assembled aggregate can be controlled by means of adding a cosurfactant. For example, the addition of SDS induced the formation of spherical micelles.

DNA↗
PubMed2005

Cell adhesion on a polymerized peptide-amphiphile monolayer.

We report the synthesis and characterization of a stable polymerized monolayer of peptide-amphihiles on a planar solid support that promotes mouse fibroblast cell adhesion and spreading. Peptide-amphiphiles consisting of a polymerizable fatty acid attached to a short RGD containing peptide sequence are self-assembled and polymerized at the water-air interface by means of the Langmuir- Blodgett technique. The surface concentration of the peptide-amphiphile is varied by co-spreading the peptide-amphiphile with an analogous non-modified polymerizable amphiphile at the water/air interface, prior to UV light-induced polymerization. The polymerized monolayer is transferred onto a hydrophobized smooth mica surface and the resulting surfaces have been investigated with respect to directing the cell adhesion and spreading of mouse fibroblast cells in a serum-free medium. Fibroblast cells adhere and spread on surfaces exposing the bioactive ligand but do not spread on reference surfaces without peptide. We find a maximum number of adherent cells at rather high peptide surface concentrations of about 10 mol% in the mixed monolayer, equivalent to more than 50 pmol/cm2 peptide on the surface of the film. We attribute this finding to a limited accessibility of the ligands by the integrins. Because of the stability of the polymerized peptide-amphiphile monolayer, these surfaces can be re-seeded multiple times with cells, i.e. adherent cells can be removed from the surface, the surface can be sterilized and cells can be re-attached.

Aluminum Silicates↗
PubMed2004

Bottom-up design of biomimetic assemblies.

Nature has evolved the ability to assemble a variety of molecules into functional architectures that can specifically bind cellular ligands. Mimicking this strategy requires the design of a set of multifaceted molecules, where elements that direct assembly were conjugated to biologically specific components. The development of functional molecular building-blocks that assemble to form compartments for therapeutics addresses the desire to have controllable morphologies that interact with biological interfaces at nanometer length scales. The practical application of such 'bottom-up' assemblies requires the ability to predict the type of aggregated structure and to synthesize molecules in a highly controlled fashion. This bottom-up approach results in a molecular platform that mimics biological systems with potential for encapsulating and delivering drug molecules.

Binding Sites↗
PubMed2004

Collective and single-molecule interactions of alpha5beta1 integrins.

A novel biomimetic system was used to study collective and single-molecule interactions of the alpha5beta1 receptor-GRGDSP ligand system with an atomic force microscope (AFM). Bioartificial membranes, which display peptides that mimic the cell adhesion domain of the extracellular matrix protein fibronectin, are constructed from peptide-amphiphiles. The interaction measured with the immobilized alpha5beta1 integrins and GRGDSP peptide-amphiphiles is specifically related to the integrin-peptide binding. It is affected by divalent cations in a way that accurately mimics the adhesion function of the alpha5beta1 receptor. The recognition of the immobilized receptor was significantly increased for a surface that presented both the primary recognition site (GRGDSP) and the synergy site (PHSRN) compared to the adhesion measured with surfaces that displayed only the GRGDSP peptide. At the collective level, the separation process of the receptor-ligand pairs is a combination of multiple unbinding and stretching events that can accurately be described by the wormlike chain (WLC) model of polymer elasticity. In contrast, stretching was not observed at the single-molecule level. The dissociation of single alpha5beta1-GRGDSP pairs under loading rates of 1-305 nN/s revealed the presence of two activation energy barriers in the unbinding process. The high-strength regime above 59 nN/s maps the inner barrier at a distance of 0.09 nm along the direction of the force. Below 59 nN/s a low-strength regime appears with an outer barrier at 2.77 nm and a much slower transition rate that defines the dissociation rate (off-rate) in the absence of force (k(off) degrees = 0.015 s(-1)).

Humans↗
PubMed2002

Adhesion and friction mechanisms of polymer-on-polymer surfaces.

The adhesion and friction of smooth polymer surfaces were studied below the glass transition temperature by use of a surface forces apparatus. The friction force of a crosslinked polymer was orders of magnitude less than that of an uncrosslinked polymer. In contrast, after chain scission of the outermost layers, the adhesion hysteresis and friction forces increase substantially. These results show that polymer-polymer adhesion hysteresis and friction depend on the dynamic rearrangement of the outermost polymer segments at shearing interfaces, and that both increase as a transition is made from crosslinked surfaces to surfaces with long chains to surfaces with quasi-free ends. The results suggest new ways for manipulating the adhesion and friction of polymer surfaces by adjusting the state of the surface chains.

Journal Article↗