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
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 […]
The lipid raft-associated protein stomatin is required for accumulation of dectin-1 in the phagosomal membrane and for full activity of macrophages against Aspergillus fumigatus.
Goldmann M, Schmidt F, Cseresnyés Z, Orasch T, Jahreis S, Hartung S, Figge MT, von Lilienfeld-Toal M, Heinekamp T, Brakhage AA
Alveolar macrophages are among the first cells to come into contact with inhaled fungal conidia of the human pathogenic fungus Aspergillus fumigatus. In lung alveoli, they contribute to phagocytosis and elimination of conidia. As a counter defense, conidia contain a grey-green pigment allowing them to survive in phagosomes of macrophages for some time. Previously, we […]
Tuning the corona-core ratio of polyplex micelles for selective oligonucleotide delivery to hepatocytes or hepatic immune cells.
Foo WL, Cseresnyés Z, Rössel C, Teng Y, Ramoji A, Chi M, Hauswald W, Huschke S, Hoeppener S, Popp J, Schacher FH, Sierka M, Figge MT, Press AT#, Bauer M#
Targeted delivery of oligonucleotides or small molecular drugs to hepatocytes, the liver’s parenchymal cells, is challenging without targeting moiety due to the highly efficient mononuclear phagocyte system (MPS) of the liver. The MPS comprises Kupffer cells and specialized sinusoidal endothelial cells, efficiently clearing nanocarriers regardless of their size and surface properties. Physiologically, this non-parenchymal shield […]