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Ligand Density (ligand + density)
Selected AbstractsCharacterization of the in vitro adherence behavior of ultrasound responsive double-shelled microspheres targeted to cellular adhesion moleculesCONTRAST MEDIA & MOLECULAR IMAGING, Issue 6 2006Susanne Ottoboni Abstract We have developed novel adhesion molecule-targeted double-shelled microspheres which encapsulate nitrogen. We report in vitro targeting studies utilizing these microspheres conjugated to target-specific antibodies directed towards ICAM-1 and VCAM-1. In static adherence experiments, the adherence patterns of microspheres conjugated to three different monoclonal antibodies (two targeted to ICAM-1 and one to VCAM-1) to their target surfaces were very different. Maximum microsphere adherence at the lowest target and/or ligand densities was observed with the VCAM-1 system. Differences in target-specific adherence were also observed between anti-ICAM-1 and anti-VCAM-1 microsphere conjugates in flow adherence studies. Equilibrium binding studies of the target proteins in solution to the microsphere-bound ligands showed that the affinity constants of two microsphere-bound monoclonal antibodies for their target proteins are similar. Thus, ligand,target affinity is not the only determinant of microsphere adherence to the target surface in our systems. Shear stress was found to have an effect on the mean diameter of adhered microspheres; a decrease in the mean diameter with increasing shear was observed. The magnitude of this effect was dependent on both microsphere-bound ligand and target surface densities, with a more pronounced change at lower densities. Adhered microspheres were readily detectable using ultrasound at the lowest tested surface density of 40,mm,2. Copyright © 2006 John Wiley & Sons, Ltd. [source] Aptamer-Conjugated Nanoparticles Efficiently Control the Activity of ThrombinADVANCED FUNCTIONAL MATERIALS, Issue 18 2010Yen-Chun Shiang Abstract Thrombin-binding aptamer-conjugated gold nanoparticles (TBA-Au NPs) for highly effective control of thrombin activity towards fibrinogen are demonstrated. While a 29-base long oligonucleotide (TBA29) has known no enzymatic inhibitory functions for thrombin-mediated coagulation, the ultrahigh anticoagulant potency of TBA29 -Au NPs can be demonstrated via the steric blocking effect, at two orders of magnitude higher than that of free TBA29. The surface aptamer density on the Au NPs is important in determining their enzymatic inhibition of thrombin and their stability in the presence of nuclease. The practicality of 100TBA29 -Au NPs (100 TBA29 molecules per Au NP) for controlling thrombin-mediated coagulation in plasma is found, and the 100TBA29 -Au NPs has an ultra binding affinity towards thrombin (Kd = 2.7 × 10,11M) due to their high ligand density. The anticoagulant activity of TBA29 -Au NPs is found to be suppressed by TBA29 complementary sequence (cTBA29) modified Au NPs (cTBA29 -Au NPs), with a suppression rate 4.6-fold higher than that of cTBA29. The easily prepared and low-cost TBA29 -Au NPs and cTBA29 -Au NPs show their potential in biomedical applications for treating various diseases related to blood clotting disorders. In principle, this study opens the possibility of regulation of molecule binding, protein recognizing, and enzyme activity by using aptamer-functionalized nanomaterials. [source] Glyconanomaterials: Synthesis, Characterization, and Ligand PresentationADVANCED MATERIALS, Issue 17 2010Xin Wang Abstract Glyconanomaterials, nanomaterials carrying surface-tethered carbohydrate ligands, have emerged and demonstrated increasing potential in biomedical imaging, therapeutics, and diagnostics. These materials combine the unique properties of nanometer-scale objects with the ability to present multiple copies of carbohydrate ligands, greatly enhancing the weak affinity of individual ligands to their binding partners. Critical to the performance of glyconanomaterials is the proper display of carbohydrate ligands, taking into consideration of the coupling chemistry, the type and length of the spacer linkage, and the ligand density. This article provides an overview of the coupling chemistry for attaching carbohydrate ligands to nanomaterials, and discusses the need for thorough characterization of glyconanomaterials, especially quantitative analyses of the ligand density and binding affinities. Using glyconanoparticles synthesized by a versatile photocoupling chemistry, methods for determining the ligand density by colorimetry and the binding affinity with lectins by a fluorescence competition assay are determined. The results show that the multivalent presentation of carbohydrate ligands significantly enhances the binding affinity by several orders of magnitude in comparison to the free ligands in solution. The effect is sizeable even at low surface ligand density. The type and length of the spacer linkage also affect the binding affinity, with the longer linkage promoting the association of bound ligands with the corresponding lectins. [source] Modeling cell adhesion to a substrate with gradient in ligand densityAICHE JOURNAL, Issue 11 2009Alireza S. Sarvestani Abstract Surface density profile of bioadhesive ligands greatly influences spreading and migration of cells on substrates. A 1D peeling model is developed to predict the equilibrium adhesion strength and peeling tension of a cell membrane, adhered on a substrate with linearly increasing density of ligands. Cell membrane is modeled as a linear elastic shell subjected to a tensile force applied at the free extremity and adhesive traction due to specific receptor-ligand interactions with the substrate. Membrane peeling tension increased with gradient slope and reached an asymptotic limit independent of gradient slope but proportional to receptor-ligand interaction energy. Peeling tension from substrates with negative gradient slope, at the rear edge of adhesion zone, was considerably lower than the tension from substrates with positive gradient slope at the leading edge, indicating that detachment is more likely to be initiated at the rear edge. This prediction leads to a possible mechanism for experimentally observed haptotactic locomotion of motile cells toward the direction of higher ligand density. © 2009 American Institute of Chemical Engineers AIChE J, 2009 [source] Thin semitransparent gels containing phenylboronic acid: porosity, optical response and permeability for sugarsJOURNAL OF MOLECULAR RECOGNITION, Issue 2 2008Alexander E. Ivanov Abstract Radical copolymerization of acrylamide (Am) (90,mol%) with N -acryloyl- m -aminophenylboronic acid (NAAPBA) (10,mol%) carried out on the surface of glass slides in aqueous solution and in the absence of chemical cross-linkers, resulted in the formation of thin semitransparent gels. The phenylboronic acid (PBA) ligand density was ca. 160,µmol/ml gel. The gels exhibited a macroporous structure and displayed optical response to sucrose, lactose, glucose and fructose in 50,mM sodium phosphate buffer, in the pH range from 6.5 to 7.5. The response was fairly reversible and linearly depended on glucose concentration in the wide concentration range from 1 to 60,mM at pH 7.3. The character of response was explained by the balance of two competing equilibrium processes: binding of glucose to phenylboronate anions and binary hydrophobic interactions of neutral PBA groups. The apparent diffusion coefficient of glucose in the gels was ca. 2.5,×,10,7,cm2/s. A freshly prepared gel can be used daily for at least 1 month without changes in sensitivity. Autoclaving (121°C, 1.2 bar, 10,min) allows for the gels sterilization, which is important for their use as glucose sensors in fermentation processes. Copyright © 2008 John Wiley & Sons, Ltd. [source] | |||||||||||||