Signal and binding. II. Converting physico-chemical responses to macromolecule-ligand interactions into thermodynamic binding isotherms.
Physico-chemical titration techniques are the most commonly used methods in characterizing molecular interactions. These methods are mainly based on spectroscopic, calorimetric, hydrodynamic, etc., measurements. However, truly quantitative physico-chemical methods are absolutely based on the determination of the relationship between the measured signal and the total average degree of binding in order to obtain meaningful interaction parameters. The relationship between the observed physico-chemical signal of whatever nature and the degree of binding must be determined and not assumed, based on some ad hoc intuitive relationship/model, leading to determination of the true binding isotherm. The quantitative methods reviewed and discussed here allow an experimenter to rigorously determine the degree of binding and the free ligand concentration, i.e., they lead to the construction of the thermodynamic binding isotherm in a model-independent fashion from physico-chemical titration curves.
Biomolecular interactions of ultrasmall metallic nanoparticles and nanoclusters
The use of nanoparticles (NPs) in biomedicine has made a gradual transition from proof-of-concept to clinical applications, with several NP types meeting regulatory approval or undergoing clinical trials. A new type of metallic nanostructures called ultrasmall nanoparticles (usNPs) and nanoclusters (NCs), while retaining essential properties of the larger (classical) NPs, have features common to bioactive proteins. This combination expands the potential use of usNPs and NCs to areas of diagnosis and therapy traditionally reserved for small-molecule medicine. Their distinctive physicochemical properties can lead to unique in vivo behaviors, including improved renal clearance and tumor distribution. Both the beneficial and potentially deleterious outcomes (cytotoxicity, inflammation) can, in principle, be controlled through a judicious choice of the nanocore shape and size, as well as the chemical ligands attached to the surface. At present, the ability to control the behavior of usNPs is limited, partly because advances are still needed in nanoengineering and chemical synthesis to manufacture and characterize ultrasmall nanostructures and partly because our understanding of their interactions in biological environments is incomplete. This review addresses the second limitation. We review experimental and computational methods currently available to understand molecular mechanisms, with particular attention to usNP–protein complexation, and highlight areas where further progress is needed. We discuss approaches that we find most promising to provide relevant molecular-level insight for designing usNPs with specific behaviors and pave the way to translational applications.
Influence of pressure and fluidization velocity on the hydrodynamics of a fluidized bed containing horizontal tubes
Abstract An experimental investigation of the influence of horizontal tubes on the bubble behaviour and through-flow velocity of gas inside bubbles was carried out and the influence of pressure and fluidization velocity was studied. The visible bubble flow rate and the gas velocity through the bubbles were measured simultaneously in a pressurized fluidized bed, using capacitance and Pitot-static pressures probes respectively. Silica sand with a mean particle diameter of 0.7 mm was fluidized at pressures between 01. and 1.6 MPa, in a bed of 0.2 × 0.3 m cross-section. Six different horizontal tube configurations were used and comparisons were made with results obtained in the same bed operated without tubes. The results from the bed with tubes show that the influence of pressure and fluidization velocity is basically the same as in the bed without tubes; an increase in pressure and fluidization velocity increases the bubble activity. At low excess gas velocities, the influence of immersed tubes on the bubble behaviour is less pronounced than at high excess gas velocities. Measurements and visual observations show that a small tube pitch gives a more uniform distribution of the visible bubble flow over the bed cross-section. At a combination of high pressure, high excess gas velocity and a large tube pitch, a preferred bubble path was observed in the centre of the bed cross-section. The pressure probe measurements show that the through-flow velocity of gas inside the bubbles is in most cases higher when tubes are present in the bed. The through-flow velocity consistently decreases with increasing pressure in the bed without tubes. The tendency is largely the same at a low excess gas velocity when tubes are present, but at a high excess gas velocity the through-flow velocity first decreases and then increases as the pressure is increased.