Biomedical subjects

Y Dori

Publications and source records attributed to Y Dori.

5 recordsLinked to original sources

PubMed2000

Ligand accessibility as means to control cell response to bioactive bilayer membranes.

We report a new method to create a biofunctional surface in which the accessibility of a ligand is used as a means to influence the cell behavior. Supported bioactive bilayer membranes were created by Langmuir-Blodgett (LB) deposition of either a pure poly(ethylene glycol) (PEG) lipid, having PEG head groups of various lengths, or 50 mol % binary mixtures of a PEG lipid and a novel collagen-like peptide amphiphile on a hydrophobic surface. The peptide amphiphile contains a peptide synthetically lipidated by covalent linkage to hydrophobic dialkyl tails. The amphiphile head group lengths were determined using neutron reflectivity. Cell adhesion and spreading assays showed that the cell response to the membranes depends on the length difference between head groups of the membrane components. Cells adhere and spread on mixtures of the peptide amphiphile with the PEG lipids having PEG chains of 120 and 750 molecular weight (MW). In contrast, cells adhered but did not spread on the mixture containing the 2000 MW PEG. Cells did not adhere to any of the pure PEG lipid membranes or to the mixture containing the 5000 MW PEG. Selective masking of a ligand on a surface is one method of controlling the surface bioactivity.

Biocompatible Materials↗

PubMed1998

Protein-like molecular architecture: biomaterial applications for inducing cellular receptor binding and signal transduction.

The development of biomaterials with desirable biocompatibility has presented a difficult challenge for tissue engineering researchers. First and foremost, materials themselves tend to be hydrophobic and/or thrombogenic in nature, and face compatibility problems upon implantation. To mediate this problem, researchers have attempted to graft protein fragments onto biomaterial surfaces to promote endothelial cell attachment and minimize thrombosis. We envisioned a novel approach, based on the capability of biomolecules to self-assemble into well-defined and intricate structures, for creating biomimetic biomaterials that promote cell adhesion and proliferation. One of the most intriguing self-assembly processes is the folding of peptide chains into native protein structures. We have developed a method for building protein-like structural motifs that incorporate sequences of biological interest. A lipophilic moiety is attached onto a N alpha-amino group of peptide chain, resulting in a "peptide-amphiphile." The alignment of amphiphilic compounds at the lipid-solvent interface is used to facilitate peptide alignment and structure initiation and propagation, while the lipophilic region absorbs to hydrophobic surfaces. Peptide-amphiphiles containing potentially triple-helical or alpha-helical structural motifs have been synthesized. The resultant head group structures have been characterized by CD spectroscopy and found to be thermally stable over physiological temperature ranges. Triple-helical peptide-amphiphiles have been applied to studies of surface modification and cell receptor binding. Cell adhesion and spreading was promoted by triple-helical peptide-amphiphiles. Cellular interaction with the type IV collagen sequence alpha 1(IV) 1263-1277 increased signal transduction, with both the time and level of induction dependent upon triple-helical conformation. Collectively, these results suggest that peptide-amphiphiles may be used to form stable molecular structure on biomaterial surfaces that promote cellular activities and improve biocompatibility.

Amino Acid Sequence↗

PubMed1997

Construction of biologically active protein molecular architecture using self-assembling peptide-amphiphiles.

The peptide-amphiphiles described here provide a simple approach for building stable protein structural motifs using peptide head groups. One of the most intriguing features of this system is the possible formation of stable lipid films on solid substrates, or the use of the novel amphiphiles in bilayer membrane systems, where the lipid tail serves not only as a peptide structure-inducing agent but also as an anchor of the functional head group in the lipid assembly. The peptide-amphiphile system potentially offers great versatility with regard to head and tail group composition and overall geometries and macromolecular structures. For building materials with molecular and cellular recognition capacity, it is essential to have a wide repertoire of tools to produce characteristic supersecondary structures at surfaces and interfaces.

Drug Design↗

PubMed1982

Lack of H-2 restriction of suppressor factor specific to myelin basic encephalitogen.

A cell-free extract has been prepared from spleen cells of (SJL/J x BALB/c)F1 mice which were rendered non-susceptible to EAE by treatment with mouse spinal cord homogenate in incomplete Freund's adjuvant. Such extract has been previously shown to have suppressive activity on the induction of EAE, as well as on the immune response in syngeneic mice towards the mouse basic protein. We have now demonstrated that this factor is as effective in several other strains of mice, of different H-2 haplotype. The activity of this factor was manifested both in vivo by inhibiting the DTH response to MBE in the various mouse strains, and in vitro, by blocking the MIF activity of the allogeneic lymphocytes. A suppressor factor was prepared by a similar procedure from the EAE-resistant BALB/c mice. This factor was as active as the factor from the (SJL/J x BALB/c)F1 hybrid in blocking the anti-MBE antibody binding to MBE. It is also suppressive, and it inhibited the DTH response to MBE in both syngeneic and semi-allogeneic (SJL/J x BALB/c)F1 mice. It is thus demonstrated that the MBE-specific soluble suppressor factor involved in the EAE system in mice shows no indication of H-2 restriction.

Animals↗

PubMed1981

Unresponsiveness to experimental allergic encephalomyelitis in mice: replacement of suppressor cells by a soluble factor.

A soluble suppressor factor has been prepared from cells of mice rendered nonsusceptible to experimental allergic encephalomyelitis (EAE) by treatment with mouse spinal cord homogenate in incomplete Freund's adjuvant. The specific activity of this factor can be augmented by using a cell population enriched on plates coated with anti-mouse Fab and the specific antigen, mouse basic encephalitogen (MBE). The resultant suppressor factor had the same biologic activities as the cells from which it originated. Thus, it suppressed specifically the delayed-type hypersensitivity (DTH) response to MBE in vivo, and blocked in vitro the effector lymphocytes that adoptively transfer the DTH response. The suppressor factor reactivity was manifested also by the capacity to suppress the activity of macrophage migration inhibition factor produced by sensitized lymphocytes in the presence of the specific antigen MBE. The suppressor factor is antigen-specific and can bind the MBE in vitro and thus compete with its antibody binding. The most significant activity of the soluble suppressor factor is its ability to interfere with the induction of clinical EAE.

Animals↗