Browsing by Author "Bhowmik, Arpan"
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Item Excitable waves and direction-sensing inᅠDictyostelium discoideum: steps towards a chemotaxis model(IOP Publishing Ltd, 2016) Bhowmik, Arpan; Rappel, Wouter-Jan; Levine, Herbert; Center for Theoretical Biological PhysicsIn recent years, there have been significant advances in our understanding of the mechanisms underlying chemically directed motility by eukaryotic cells such as Dictyostelium. In particular, the local excitation and global inhibition (LEGI) model has proven capable of providing a framework for quantitatively explaining many experiments that present Dictyostelium cells with tailored chemical stimuli and monitor their subsequent polarization. In their natural setting, cells generate their own directional signals via the detection and secretion of cyclic adenosine monophosphate (cAMP). Here, we couple the LEGI approach to an excitable medium model of the cAMP wave-field that is propagated by the cells and investigate the possibility for this class of models to enable accurate chemotaxis to the cAMP waveforms expected in vivo. Our results indicate that the ultra-sensitive version of the model does an excellent job in providing natural wave rectification, thereby providing a compelling solution to the 'back-of-the-wave paradox' during cellular aggregation.Item Inter-Cellular Communication and Pattern Formation: An investigation of Cellular Signaling and Cooperation(2018-04-13) Bhowmik, Arpan; Levine, HerbertIn this project, we will be presenting modeling approaches to study cellular signaling and the resulting physiological phenomena. We will study chemotaxis in dictyostelium discoideum, a model system in which single autonomous cells communicate with each other and aggregate into cellular mounds containing thousands of cells in response to starvation (chemotaxis quite literally implies “motion (taxis) in response to chemical substances (chemo)”). Here our focus will be on developing phenomenological models to describe cellular behavior; we will not detail the molecular machinery behind any cellular process (which is a complicated endeavor), but rather test the viability of simulating complex chemical networks with simple physical models. Secondly, we will focus on the Notch signaling pathway. This pathway is implicated in a diverse group of phenomena where cells pick a “fate” based on its neighbors. Here, signaling is mediated by contact with neighbors, as opposed to a diffusive signal in chemotaxis, as such we are focused closely on the dependence of outcome (patterns of cells with different fates) on network architecture (i.e. the types of players involved and types of interaction between chemical players) and cellular geometry. These projects exemplify the use of simple models and numerical algorithms to simulate biological processes to develop an understanding of how network architecture relate to cellular behavior. As we understand better how cells change fate and direct their motion, we can better understand such phenomena as immune responses, bacterial colony dynamics, inflammation and wound healing as well as cancer metastasis.