In this study we investigate receptor–ligand binding in the context of antibody–antigen binding. We established a quantitative mapping between macroscopic binding rates of a deterministic differential equation model and their microscopic equivalents as obtained from simulating the spatiotemporal binding kinetics by a stochastic agent-based model. Furthermore, various properties of B cell-derived receptors like their dimensionality of motion, morphology, and binding valency are considered and their impact on receptor–ligand binding kinetics is investigated. The different morphologies of B cell-derived receptors include simple sperical representations as well as more realistic Y-shaped morphologies. These receptors move in different dimensionalities, i.e. either as membrane-anchored receptors or as soluble antibodies. The mapping of the macroscopic and microscopic binding rates allowed us to quantitatively compare different agent-based model variants for the different types of B cell-derived receptors. Our results indicate that the dimensionality of motion governs the binding kinetics and that this predominant impact is quantitatively compensated by the bivalency of these receptors.
Model for antigen binding by B cell-derived receptors
Publications
Guided-deconvolution for correlative light and electron microscopy
Ma F, Kaufmann R, Sedzicki J, Cseresnyés Z, Dehio C, Hoeppener S, Figge MT, Heintzmann R
Surrogate infection model predicts optimal alveolar macrophage number for clearance of Aspergillus fumigatus infections.
Saffer C, Timme S, Rudolph P, Figge MT# (2023) NPJ Syst Biol Appl 9, 12.
The immune system has to fight off hundreds of microbial invaders every day, such as the human-pathogenic fungus Aspergillus fumigatus. The fungal conidia can reach the lower respiratory tract, swell and form hyphae within six hours causing life-threatening invasive aspergillosis. Invading pathogens are continuously recognized and eliminated by alveolar macrophages (AM). Their number plays an […]
Aspergillus fumigatus hijacks human p11 to redirect fungal-containing phagosomes to non-degradative pathway.
Jia LJ, Rafiq M, Radosa L, Hortschansky P, Cunha C, Cseresnyés Z, Krüger T, Schmidt F, Heinekamp T, Straßburger M, Loeffler B, Doenst T, Lacerda JF, Campos A, Figge MT, Carvalho A, Kniemeyer O, Brakhage AA
The decision whether endosomes enter the degradative or recycling pathway in mammalian cells is of fundamental importance for pathogen killing, and its malfunctioning has pathological consequences. We discovered that human p11 is a critical factor for this decision. The HscA protein present on the conidial surface of the human-pathogenic fungus Aspergillus fumigatus anchors p11 on […]