Biomedical subjects

B A Waite

Publications and source records attributed to B A Waite.

3 recordsLinked to original sources

PubMed1993

An idealized dynamical model of simple diffusional interactions between macromolecules and between macromolecules and surfaces.

A model for hard-sphere, nonelectrostatic diffusional interactions between macromolecules and between macromolecules and surfaces is presented. Quantities such as average free path and impact frequency are derived, being validated by full three-dimensional simulations of large numbers of random flights. A method for obtaining the total collision rate is developed based on absorption boundary conditions applied to the time-independent diffusion equation, multiplied by the probable number of subsequent encounters. A distribution function is obtained that describes both the spatial and temporal impact profiles of diffusing molecules with surfaces as well as the detailed nature of individual encounters. Conclusions are that the interaction of diffusing macromolecules with surfaces is an extremely efficient process; trajectories are typified by clusters of relatively closely spaced encounters separated by relatively long excursions prior to reimpact. Results should be applicable to the development of kinetic models for describing such complex phenomena as ligand binding to receptors on cell surfaces.

Cell Membrane↗

PubMed1988

Antibody multivalency effects in the direct binding model for vesicle immunolysis assays.

An extension of a previous model of liposome-based immunoassays is presented which incorporates the effects of antibody multivalency in the binding process. Equations based on the distribution of vesicles having both mono- and divalently bound species show the quantitative relationships of the experimental parameters, including vesicle concentration, antigen density on vesicle surfaces, antibody concentration, and antibody affinity (both for the initial binding step and for the subsequent cross-linking step). It is found that in the case of low antibody concentration, the multivalent model can be cast in the form of the previously described monovalent model, replacing the association equilibrium constant with an effective equilibrium constant which is found to depend linearly on the lateral antigen density and on the valency of the binding antibody. Comparisons to certain experiments are made using this more realistic model of complement-mediated vesicle immunoassay. For the case of IgM binding, it is estimated that as few as 1000 antibody molecules can be detected in a typical lytic assay, representing a significant increase in sensitivity over previous predictions.

Animals↗

PubMed1987

Analysis of vesicle immunolysis assays. The direct binding model.

Assays based on lysis of lipid vesicles have shown high sensitivity. However, little as yet is known about the quantitative relationships among the various assay parameters, due in part to the lack of a predictive theoretical model. This paper presents the derivation of the equations that describe a simple model assay system in terms of the total fraction of vesicles with bound antibodies and the distribution of vesicles with one, two, or more antibodies bound. The equations show how the binding of antibodies to vesicles is affected by such variables as: vesicle concentration, antigen density on vesicle surfaces, antibody concentration, and antibody affinity. With the distribution functions, experiments can be designed to determine the minimum number of antibodies needed to lyse a vesicle. In addition, it is shown how estimations of the ultimate sensitivity of lipid vesicle lytic assays can be made. The model can be used to optimize vesicle lysis assay systems.

Antigen-Antibody Reactions↗