Biomedical subjects

Michael Meyer-Hermann

Publications and source records attributed to Michael Meyer-Hermann.

9 recordsLinked to original sources

PubMed2006

Geometrically repatterned immunological synapses uncover formation mechanisms.

The interaction of T cells and antigen-presenting cells is central to adaptive immunity and involves the formation of immunological synapses in many cases. The surface molecules of the cells form a characteristic spatial pattern whose formation mechanisms and function are largely unknown. We perform computer simulations of recent experiments on geometrically repatterned immunological synapses and explain the emerging structure as well as the formation dynamics. Only the combination of in vitro experiments and computer simulations has the potential to pinpoint the kind of interactions involved. The presented simulations make clear predictions for the structure of the immunological synapse and elucidate the role of a self-organizing attraction between complexes of T cell receptor and peptide-MHC molecule, versus a centrally directed motion of these complexes.

Antigen-Presenting Cells↗

PubMed2006

Continuum versus discrete model: a comparison for multicellular tumour spheroids.

We study multicellular tumour spheroids with a continuum model based on partial differential equations (PDEs). The model includes viable and necrotic cell densities, as well as oxygen and glucose concentrations. Viable cells consume nutrients and become necrotic below critical nutrient concentrations. Proliferation of viable cells is contact-inhibited if the total cellular density locally exceeds volume carrying capacity. The model is discussed under the assumption of spherical symmetry. Unknown model parameters are determined by simultaneously fitting the cell number to several experimental growth curves for different nutrient concentrations. The outcome of the PDE model is compared with an analogous off-lattice agent-based model for tumour growth. It turns out that the numerically more efficient PDE model suffices to explain the macroscopic growth data. As in the agent-based model, we find that the experimental growth curves are only reproduced when a necrotic core develops. However, evaluation of morphometric properties yields differences between the models and the experiment.

Animals↗

PubMed2005

Multicellular tumor spheroid in an off-lattice Voronoi-Delaunay cell model.

We study multicellular tumor spheroids by introducing a new three-dimensional agent-based Voronoi-Delaunay hybrid model. In this model, the cell shape varies from spherical in thin solution to convex polyhedral in dense tissues. The next neighbors of the cells are provided by a weighted Delaunay triangulation with on average linear computational complexity. The cellular interactions include direct elastic forces and cell-cell as well as cell-matrix adhesion. The spatiotemporal distribution of two nutrients--oxygen and glucose--is described by reaction-diffusion equations. Viable cells consume the nutrients, which are converted into biomass by increasing the cell size during the G1 phase. We test hypotheses on the functional dependence of the uptake rates and use computer simulations to find suitable mechanisms for the induction of necrosis. This is done by comparing the outcome with experimental growth curves, where the best fit leads to an unexpected ratio of oxygen and glucose uptake rates. The model relies on physical quantities and can easily be generalized towards tissues involving different cell types. In addition, it provides many features that can be directly compared with the experiment.

Animals↗

PubMed2005

Identification of B and T cells in human spleen sections by infrared microspectroscopic imaging.

BACKGROUND: Infrared spectroscopy probes the chemical composition and molecular structure of complex systems such as tissue and cells. Infrared spectroscopic imaging combines this spectral information with lateral resolution near the single-cell level. We analyzed whether this method is competitive with classic immunohistochemical methods for immunologic tissue and cells. METHODS: We recorded infrared microspectroscopic mapping datasets with a 90- x 90-microm2 aperture from a 3- x 3-mm2 unstained tissue area of human spleen. A secondary follicle containing a germinal center and a T zone were studied in more detail by infrared microspectroscopic imaging with lateral resolution near 5 mum. The results were compared with consecutive sections stained by immunoglobulin D antibodies. T and B lymphocytes were extracted from human blood and served as independent test samples. RESULTS: Cluster analysis of infrared datasets produced images that distinguished anatomical features such as primary and secondary follicles, T zones, arteries, and spleen red pulp. The assignments could be confirmed in consecutive sections by immunohistochemical staining. Main spectral variances between T and B lymphocytes in high-resolution measurements were attributed to specific spectral contributions of DNA and cytosol. CONCLUSIONS: Sensitivity and specificity of the infrared based methods are comparable to those of standard staining procedures for identification of B and T cells. However, infrared spectroscopic imaging can offer advantages in velocity, data throughput, and standardization because of minimal sample preparation. The results emphasize the potential of infrared spectroscopy as an innovative tool for the distinction of cell types, in particular in immunologic tissue.

Adolescent↗

PubMed2004

The type of seeder cells determines the efficiency of germinal center reactions.

During humoral immune responses some germinal centers (GCs) develop very well and give rise to a large number of high affinity antibody producing plasma cells. Other GC reactions develop poorly, somatic mutation is reduced, and the output production is practically absent. This led to the hypothesis that two classes of GCs exist, and that GCs show an all-or-none behaviour. We investigate the role of the seeder B cells affinity to the antigen in this context. It is shown in the framework of a space-time simulation of GC reactions that, indeed, the seeder cell affinity is a critical parameter that determines the fate of the GC reaction. Starting from a homogeneous distributions of seeder cell affinities in an ensemble of GC reactions, we demonstrate that an all-or-none behaviour of GCs has to be expected. Possible implications are discussed.

Animals↗

PubMed2002

A mathematical model for the germinal center morphology and affinity maturation.

During germinal center reactions, the appearance of two specific zones are observed: the dark and the light zone. Up to now, the origin and function of these zones are poorly understood. In the framework of a stochastic and discrete model, several possible pathways of zone development during germinal center reactions are investigated. The importance of the zones in the germinal center for affinity maturation, i.e. the process of antibody optimization is discussed.

Animals↗

PubMed2002

Does recycling in germinal centres exist?

A general criterion is formulated to decide if the recycling of B cells exists in germinal centre (GC) reactions. The criterion is independent of the selection and affinity maturation process and based solely on total centroblast population arguments. An experimental test is proposed to verify whether the criterion is fulfilled.

Animals↗

PubMed2002

Conclusions from two model concepts on germinal center dynamics and morphology.

Germinal centers (GC) are an essential part of the humoral immune response. They develop a clear structure during maturation: Centroblasts and centrocytes are separated into two zones, the dark and the light zone. The mechanisms leading to this specific morphology as well as the reason for zone-depletion during a later phase of the GC reaction have not clearly been revealed in experiment. We discuss and weigh possible mechanisms of dark and light zone development in the framework of two mathematical models. In a comparative approach we formulate constraints on typical lymphocyte velocities in GCs which are characteristic for the different proposed mechanisms.

B-Lymphocytes↗

PubMed2002

A possible role of chemotaxis in germinal center formation.

During the germinal center (GC) reaction a characteristic morphology is developed. In the framework of a recently developed space-time model for the GC, a mechanism for the formation of dark and light zones has been proposed. There, the mechanism is based on a diffusing differentiation signal which is distinguished by follicular dendritic cells (FDC). Here, we investigate a possible influence of recently found chemoattractants on GC formation in the framework of a single cell-based stochastic and discrete three-dimensional model. This necessitates a more detailed spatial description. The model is enlarged by a detailed prescription of cell motility and it is introduced as a consistent volume concept. We consider various possible chemotactic pathways that may play a role for the development of both zones. Our results suggest that the centrocyte motility resulting from a FDC-derived chemoattractant has to exceed a lower limit to allow the separation of centroblasts and centrocytes. In contrast to light microscopy, the dark zone is ring shaped. This suggests that FDC-derived chemoattractants alone cannot explain the typical GC morphology.

Antigen-Antibody Reactions↗