Biology subjects
Publications and source records attributed to Rieger, H..
We explored the application of the adaption algorithm introduced by Secomb et. al. to artificial blood vessel networks and find that the resulting networks to not obey Murrays law. The reported analysis and visual examples document the contrast between two different types of networks. We conjecture that an interrupt of an established signaling cascade could be a hallmark of solid vascular tumors.
Release of Ca2+ from endoplasmatic retriculum (ER) Ca2+ stores causes stromal interaction molecules (STIM) in the ER membrane and ORAI proteins in the plasma membrane (PM) to interact and form the Ca2+ release activated Ca2+ (CRAC) channels, which represent a major Ca2+ entry route in non-excitable cells and thus control various cell functions. Extracellular reactive oxygen species (ROS) can modulate the CRAC current Icrac via oxidation of ORAI1. We formulate a reaction-diffusion model to quantify the STIM1-ORAI1 interaction during CRAC channel formation and analyze different ORAI1 channel stoichiometries and different ratios of STIM1 and ORAI1 in comparison with experimental data. We incorporate the inhibition of ORAI1 channels by ROS into our model and calculate its contribution to the CRAC channel amplitude. We find that the possibility of reactions between CRAC channel subunits and established CRAC channels tunes the total amount of Ca2+ influx and determines which CRAC channel configuration is mostly preferred. High numbers of ROS-inhibited ORAI1 dimers (in comparison to non-inhibited ORAI1 dimers) are needed to induce a strong decrease of Ca2+ influx compared to the wildetype (WT) case.
During the past years our group published several articles using computer simulations to address the complex interaction of tumors and the vasculature as underlying transport network. Advances in imaging and lab techniques pushed in vitro research of tumor spheroids forward and animal models as well as clinical studies provided more insights to single processes taking part in tumor growth, however, an overall picture is still missing. Computer simulations are a none-invasive option to cumulate current knowledge and form a quasi in vivo system. In our software, several known models were assembled into a multi-scale approach which allows to study length scales relevant for clinical applications.\n\nWe release our code to the public domain, together with a detailed description of the implementation and several examples, with the hope of usage and futher development by the community. Justification for the included algorithms and the biological models was obtained in previous publications, here we summarize technical aspects following the workflow of a typical simulation procedure.
The efficiency of intracellular cargo transport from specific source to target locations is strongly dependent upon molecular motor-assisted motion along the cytoskeleton. Radial transport along microtubules and lateral transport along the filaments of the actin cortex underneath the cell membrane are characteristic for cells with a centrosome. The interplay between the specific cytoskeleton organization and the motor performance realizes a spatially inhomogeneous intermittent search strategy. In order to analyze the efficiency of such intracellular search strategies we formulate a random velocity model with intermittent arrest states. We evaluate efficiency in terms of mean first passage times for three different, frequently encountered intracellular transport tasks: i) the narrow escape problem, which emerges during cargo transport to a synapse or other specific region of the cell membrane, ii) the reaction problem, which considers the binding time of two particles within the cell, and iii) the reaction-escape problem, which arises when cargo must be released at a synapse only after pairing with another particle. Our results indicate that cells are able to realize efficient search strategies for various intracellular transport tasks economically through a spatial cytoskeleton organization that involves only a narrow actin cortex rather than a cell body filled with randomly oriented actin filaments.