PubMed Health⌕ Search

Biomedical subjects

Efrosini Kokkoli

Publications and source records attributed to Efrosini Kokkoli.

11 recordsLinked to original sources
PubMed2006

Mechanistic principles of nanoparticle evolution to zeolite crystals.

Precursor nanoparticles that form spontaneously on hydrolysis of tetraethylorthosilicate in aqueous solutions of tetrapropylammonium (TPA) hydroxide evolve to TPA-silicalite-1, a molecular-sieve crystal that serves as a model for the self-assembly of porous inorganic materials in the presence of organic structure-directing agents. The structure and role of these nanoparticles are of practical significance for the fabrication of hierarchically ordered porous materials and molecular-sieve films, but still remain elusive. Here we show experimental findings of nanoparticle and crystal evolution during room-temperature ageing of the aqueous suspensions that suggest growth by aggregation of nanoparticles. A kinetic mechanism suggests that the precursor nanoparticle population is distributed, and that the 5-nm building units contributing most to aggregation only exist as an intermediate small fraction. The proposed oriented-aggregation mechanism should lead to strategies for isolating or enhancing the concentration of crystal-like nanoparticles.

Journal Article↗
PubMed2006

Design of a novel fibronectin-mimetic peptide-amphiphile for functionalized biomaterials.

The interaction of the alpha5beta1 integrin with its ligand, fibronectin, supports numerous adhesive functions and has an important role in health and disease. In recent years, there has been a considerable effort in designing fibronectin-mimetic peptides to target the integrin. However, to date, the therapeutic use of these peptides has been limited, as they cannot accurately mimic fibronectin's binding affinity for alpha5beta1. A peptide-amphiphile (PR_b) was synthesized with a peptide headgroup composed of four building blocks: a spacer; RGDSP, the primary recognition site for alpha5beta1; PHSRN, the synergy binding site; and a linker. The linker was designed to mimic two important criteria: the distance and the hydrophobicity/hydrophilicity between PHSRN and RGD in fibronectin. Human umbilical vein endothelial cells were seeded on different substrates and evaluated in terms of adhesion, spreading, specificity, cytoskeleton organization, focal adhesions, and secretion of extracellular fibronectin. This peptide was shown to perform comparably to fibronectin, indicating that a biomimetic approach can result in the design of novel peptides with therapeutic potential for biomaterial functionalization.

Biomimetic Materials↗
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↗
PubMed2005

Patterned biomimetic membranes: effect of concentration and pH.

Planar-supported lipid bilayers have attracted enormous attention because of their properties as model cell membranes, which can be employed in a variety of fundamental biological studies and medical devices. Furthermore, the development of patterned biological interfaces is of great practical and scientific interest because of their potential applications in the field of biosensors, drug screening, tissue engineering, and medical implants. In this study, mica-supported membranes were constructed from biomimetic peptide-amphiphiles and their mixtures with lipidated poly(ethylene glycol) (PEG120) molecules or 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) phospholipids using the Langmuir-Blodgett technique. The two peptide-amphiphiles used in this study were a fibronectin-mimetic with the PHSRN(SG)(3)SGRGDSP headgroup (referred to as PHSRN-GRGDSP) that contains both the primary (GRGDSP) and the synergy (PHSRN) recognition sites for alpha(5)beta(1) integrins and a peptide-amphiphile that mimics a fragment of the N-terminus of the fractalkine receptor (referred to as NTFR). Compression isotherms of the peptide-amphiphiles and their mixtures with PEG120 at the air/water interface were recorded and analyzed to evaluate the extent of miscibility in the two-component LB films. Domain formation in mica-supported bilayers constructed from mixtures of peptide-amphiphiles and lipidated PEG120 or DPPC was observed using atomic force microscopy. In PHSRN-GRGDSP/PEG120 mixtures deposited from an aqueous subphase at pH 7, concentration-dependent phase separation was observed on the AFM images. The NTFR/PEG120 and NTFR/DPPC mixtures deposited at pH 10 exhibited extensive lateral phase separation at all mixture compositions, whereas at deposition pH 7 the concentrations of NTFR/DPPC examined here were well mixed.

1,2-Dipalmitoylphosphatidylcholine↗
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↗
PubMed2003

Microstructural optimization of a zeolite membrane for organic vapor separation.

A seeded growth method for the fabrication of high-permeance, high-separation-factor zeolite (siliceous ZSM-5, [Si96O192]-MFI) membranes is reported. The method consists of growing the crystals of an oriented seed layer to a well-intergrown film by avoiding events that lead to a loss of preferred orientation, such as twin overgrowths and random nucleation. Organic polycations are used as zeolite crystal shape modifiers to enhance relative growth rates along the desirable out-of-plane direction. The polycrystalline films are thin (approximately 1 micrometer) with single grains extending along the film thickness and with large in-plane grain size (approximately 1 micrometer). The preferred orientation is such that straight channels with an open diameter of approximately 5.5 angstroms run down the membrane thickness. Comparison with previously reported membranes shows that these microstructurally optimized films have superior performance for the separation of organic mixtures with components that have small differences in size and shape, such as xylene isomers.

Journal Article↗
PubMedDate not supplied

Biomimetic peptide-amphiphiles for functional biomaterials: the role of GRGDSP and PHSRN.

The study we present involves the use of a biomimetic system that allows us to study specific interactions in the alpha(5)beta(1) receptor-GRGDSP ligand system with an atomic force microscope (AFM). Bioartificial membranes that mimic the adhesion domain of the extracellular matrix protein fibronectin are constructed from peptide-amphiphiles. A novel peptide-amphiphile is designed that contains both GRGDSP (Gly-Arg-Gly-Asp-Ser-Pro, the primary recognition site for alpha(5)beta(1)) and PHSRN (Pro-His-Ser-Arg-Asn, the synergy binding site for alpha(5)beta(1)) sequences in a single peptide formulation, separated by a spacer. Two different antibodies are used to immobilize and activate isolated alpha(5)beta(1) integrins on the AFM tip. The interaction measured between immobilized alpha(5)beta(1) integrins and peptide-amphiphiles is specific for integrin-peptide binding and is affected by divalent cations in a way that accurately mimics the adhesion function of the alpha(5)beta(1) receptor. The strength of the PHSRN synergistic effect depends on the accessibility of this sequence to alpha(5)beta(1) integrins. An increase in adhesion is observed compared to surfaces displaying only GRGDSP peptides when the new biomimetic peptide-amphiphiles are diluted with lipidated poly(ethylene glycol), which provides more space for the peptide headgroups to bend and expose more of the PHSRN at the interface.

Amino Acid Sequence↗
PubMedDate not supplied

Fractalkine targeting with a receptor-mimicking peptide-amphiphile.

In this study we have designed the NTFR peptide-amphiphile that mimics a fragment of the N-terminus of the fractalkine receptor (CX(3)CR1) and specifically targets fractalkine, a novel adhesion molecule expressed on the surface of inflamed endothelial cells. Bioartificial membranes were constructed from mixtures of NTFR peptide-amphiphiles and DPPC (1,2-dipalmitoyl-sn-glycero-3-phosphocholine) phospholipids, and the affinity and specificity of fractalkine for the synthetic NTFR was investigated with an atomic force microscope (AFM). Fractalkine was immobilized onto the AFM tips, and forces were collected between fractalkine and the bioartificial membranes. The adhesive interactions were studied at the collective level, when each adhesion event corresponded to the rupture of multiple biomolecular bonds. Retraction force profiles for the fractalkine-NTFR system exhibited single or multiple peaks and a small percentage of the force curves demonstrated stretching of the fractalkine-NTFR complex. Strong adhesion was measured when both DPPC and NTFR were present, compared to pure NTFR surfaces. This may be due to the fact that the DPPC molecule is shorter, and thus it can provide more space for the peptide headgroup to bend and expose its sequence at the interface. Specificity was demonstrated by comparing the NTFR-fractalkine adhesion to the forces between the alpha(5)beta(1) integrin (an adhesion receptor expressed on the surface of endothelial cells) and other surfaces such as GRGDSP (the specific ligand for alpha(5)beta(1)), GRGESP (an inactive sequence), and NTFR.

CX3C Chemokine Receptor 1↗