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A Density-Dependent Switch Drives Stochastic Clustering and Polarization of Signaling Molecules

Alexandra Jilkine, Sigurd B. Angenent, Lani F. Wu, Steven J. Altschuler, Mark S. Alber
2011 PLoS Computational Biology  
Regulating the density of signaling molecules provides a simple mechanism for a positive feedback circuit to robustly switch between clustered and un-clustered states.  ...  Here, we show that a minimal positive feedback circuit provides the general principle for both suppressing and amplifying noise: below a critical density of signaling molecules, clustering switches off  ...  Curves correspond to n à Supporting Information for ''A Density-Dependent Switch Drives Stochastic Clustering and Polarization of Signaling Molecules'', containing details of mathematical derivations  ... 
doi:10.1371/journal.pcbi.1002271 pmid:22102805 pmcid:PMC3213192 fatcat:z65plogmsnforbi7fcm3azgj4u

On the spontaneous emergence of cell polarity

Steven J. Altschuler, Sigurd B. Angenent, Yanqin Wang, Lani F. Wu
2008 Nature  
We find that the polarization frequency has an inverse dependence on the number of signalling molecules: the frequency of polarization decreases as the number of molecules becomes large.  ...  We identify an intrinsic stochastic mechanism through which positive feedback alone is sufficient to account for the spontaneous establishment of a single site of polarity.  ...  Crews for latrunculin A and Rong Li for the yeast strain.  ... 
doi:10.1038/nature07119 pmid:18704086 pmcid:PMC2562338 fatcat:s67zvvq3sbfsfdy7d56qezt4pq

Spatiotemporal regulation of chemical reactions by active cytoskeletal remodeling

A. Chaudhuri, B. Bhattacharya, K. Gowrishankar, S. Mayor, M. Rao
2011 Proceedings of the National Academy of Sciences of the United States of America  
In general such cytoskeletal driven clustering of proteins could be a cellular mechanism to spatiotemporally regulate and amplify local chemical reaction rates in a variety of contexts such as signaling  ...  We show how the interplay between active contractility and remodeling of the cytoskeleton can result in transient focusing of passive molecules to form clusters, leading to a dramatic increase in the reaction  ...  This actin-dependent resetting could be relevant for the signaling specificity of the promiscuous Ras-family proteins that make actin-dependent clusters (8) .  ... 
doi:10.1073/pnas.1100007108 pmid:21873247 pmcid:PMC3169122 fatcat:yqwx52bhwveqbnfrvlz2dbwcny

Spatial and temporal signal processing and decision making by MAPK pathways

Oguzhan Atay, Jan M. Skotheim
2017 Journal of Cell Biology  
More generally, a new wave of quantitative single-cell studies has begun to elucidate how signaling dynamics determine cell physiology and represents a paradigm shift from descriptive to predictive biology  ...  Recent developments show how MAPK pathways perform exquisite spatial and temporal signal processing and underscores the importance of studying the dynamics of signaling pathways to understand their physiological  ...  This work was supported by the National Institutes of Health through grant R01GM092925 to J.M. Skotheim and a Stanford University Interdisciplinary Graduate Fellowship to O. Atay.  ... 
doi:10.1083/jcb.201609124 pmid:28043970 pmcid:PMC5294789 fatcat:q32qjzcnnvgv7mlje7qcn3xfqu

Boolean model of anchorage dependence and contact inhibition points to coordinated inhibition but semi-independent induction of proliferation and migration

Eric Guberman, Hikmet Sherief, Erzsébet Ravasz Regan
2020 Computational and Structural Biotechnology Journal  
Here we propose a Boolean regulatory network model that synthesizes mechanosensitive signaling that links anchorage to a matrix of varying stiffness and cell density sensing to contact inhibition, proliferation  ...  of cell density and mitogenic stimulation.  ...  research sabbatical program; the College of Wooster's Independent Study program that allowed EG to dedicate a considerable portion of his senior year to this project; the College of Wooster's sophomore  ... 
doi:10.1016/j.csbj.2020.07.016 pmid:32913583 pmcid:PMC7451872 fatcat:4dpkc5i6mrdflnwr6qwrx553x4

MOLNs: A Cloud Platform for Interactive, Reproducible, and Scalable Spatial Stochastic Computational Experiments in Systems Biology Using PyURDME

Brian Drawert, Michael Trogdon, Salman Toor, Linda Petzold, Andreas Hellander
2016 SIAM Journal on Scientific Computing  
In this paper, we present PyURDME, a new, user-friendly spatial modeling and simulation package, and MOLNs, a cloud computing appliance for distributed simulation of stochastic reaction-diffusion models  ...  This results in a barrier to the adoption of spatial stochastic simulation tools, effectively limiting the type of biological questions addressed by quantitative modeling.  ...  The content of this paper is solely the responsibility of the authors and does not necessarily represent the official views of these agencies. We would like to acknowledge Benjamin B.  ... 
doi:10.1137/15m1014784 pmid:28190948 pmcid:PMC5302863 fatcat:4bu72sojnnhrnh43mjmjkbs5hi

MOLNs: A cloud platform for interactive, reproducible and scalable spatial stochastic computational experiments in systems biology using PyURDME [article]

Brian Drawert and Michael Trogdon and Salman Toor and Linda Petzold and Andreas Hellander
2015 arXiv   pre-print
In this paper, we present PyURDME, a new, user-friendly spatial modeling and simulation package, and MOLNs, a cloud computing appliance for distributed simulation of stochastic reaction-diffusion models  ...  This results in a barrier to the adoption of spatial stochastic simulation tools, effectively limiting the type of biological questions addressed by quantitative modeling.  ...  BD and AH developed the software; BD and AH conceived and designed the study; BD, MT, ST, and AH performed the experiments and data analysis; all authors wrote the manuscript. Conflict of interest.  ... 
arXiv:1508.03604v1 fatcat:cmcdplhygrh7bnlndz4x7s3gfi

Diffusion-limited phase separation in eukaryotic chemotaxis

A. Gamba, A. de Candia, S. Di Talia, A. Coniglio, F. Bussolino, G. Serini
2005 Proceedings of the National Academy of Sciences of the United States of America  
Here, we propose that directional sensing is the consequence of a phase-ordering process mediated by phosphoinositide diffusion and driven by the distribution of chemotactic signal.  ...  In this framework, large reversible amplification of shallow chemotactic gradients, selective localization of chemical factors, macroscopic response timescales, and spontaneous polarization arise naturally  ...  f s and a local (site dependent) probability p i s .  ... 
doi:10.1073/pnas.0503974102 pmid:16291809 pmcid:PMC1287969 fatcat:wqrpdizmivhynjswk55o3konry

Stochastic transitions in a bistable reaction system on the membrane

M. Kochanczyk, J. Jaruszewicz, T. Lipniacki
2013 Journal of the Royal Society Interface  
Transitions between steady states of a multi-stable stochastic system in the perfectly mixed chemical reactor are possible only because of stochastic switching.  ...  The activating wave can be induced after a small subdomain is activated as a result of a stochastic fluctuation.  ...  It has been shown that the self-recruitment of cytoplasmic proteins to the cell membrane leads to the generation of a single cluster of active molecules and thus may define a unique axis of cell polarity  ... 
doi:10.1098/rsif.2013.0151 pmid:23635492 pmcid:PMC3673150 fatcat:mztjhfozobeqflpzre533z2ybi

Spatial signal amplification in cell biology: A lattice-gas model for self-tuned phase ordering

T. Ferraro, A. de Candia, A. Gamba, A. Coniglio
2008 Europhysics letters  
Experiments show that the movement of eukaryotic cells is regulated by a process of phase separation of two competing enzymes on the cell membrane, that effectively amplifies shallow external gradients  ...  Notably, the cell is able to self-tune the final enzyme concentrations to an equilibrium state of phase coexistence, for a wide range of the average attractant concentration.  ...  of signaling molecules.  ... 
doi:10.1209/0295-5075/83/50009 fatcat:3cgneywmkve2hgdhxjmawg62eu

Quantitative Approaches to Heterogeneity and Growth Variability in Cell Populations [chapter]

Priscilla Macansantos, Vito Quaranta
2014 Managing Complexity, Reducing Perplexity  
Our aim is to highlight a few stimulating examples from this fledgling and exciting field, in order to frame the issue and point to challenges and opportunities that lie ahead.  ...  Clearly, a mathematical theory of cellular heterogeneity could have fundamental implications.  ...  Acknowledgments We would like to thank the contributors of data included: Fig. 1  ... 
doi:10.1007/978-3-319-03759-2_2 fatcat:ekcx4f43grezjak3tdzbxxgbji

Lens-based fluorescence nanoscopy

Christian Eggeling, Katrin I. Willig, Steffen J. Sahl, Stefan W. Hell
2015 Quarterly Reviews of Biophysics (print)  
or 'nanoscopy' offers opportunities to study problems in biophysical and biomedical research at a new level of detail.  ...  Usually these are fluorescent 'on' and 'off' states causing the adjacent molecules to emit sequentially in time.  ...  Finally, one of us (SWH) acknowledges long-term support by a Gottfried Wilhelm Leibniz Prize of the Deutsche Forschungsgemeinschaft, the Körber European Science Prize of the Körber Foundation and by the  ... 
doi:10.1017/s0033583514000146 pmid:25998828 fatcat:uzri3hvwevdlhcpogmsjqqq554

Optical Nanoscopy: From Acquisition to Analysis

Travis J. Gould, Samuel T. Hess, Joerg Bewersdorf
2012 Annual Review of Biomedical Engineering  
By exploiting photophysical properties of fluorescent probe molecules, this new class of methods yields a resolving power that is fundamentally diffraction unlimited.  ...  Furthermore, we provide an overview of existing analysis strategies and discuss their application.  ...  Acknowledgments We thank Edward Allgeyer and Fang Huang for helpful comments on the manuscript. T.J.  ... 
doi:10.1146/annurev-bioeng-071811-150025 pmid:22559319 pmcid:PMC3568761 fatcat:rfgeh3ecbjddloi2qnkp736q3i

Visualizing Cell Structure and Function with Point-Localization Superresolution Imaging

Prabuddha Sengupta, Schuyler Van Engelenburg, Jennifer Lippincott-Schwartz
2012 Developmental Cell  
ACKNOWLEDGMENTS We thank Alan Hoofring (National Institutes of Health Medical Arts Design Section) for help with the illustrations.  ...  The approaches are enabling quantification of different parameters of single-molecule spatial organization, including the presence of molecule clusters, their size, density, and abundance in a particular  ...  The molecules included signaling molecules LAT and Lyn, a lipid-anchored GPI protein, and the viral protein VSVG.  ... 
doi:10.1016/j.devcel.2012.09.022 pmid:23237943 pmcid:PMC4221848 fatcat:uhwzk7rxcfe5tbxeyx7er2jxya

A Bistable Model of Cell Polarity

Matteo Semplice, Andrea Veglio, Giovanni Naldi, Guido Serini, Andrea Gamba, Masaru Katoh
2012 PLoS ONE  
Here we suggest that bistability of ultrasensitive signaling pathways in a diffusive environment provides a basic mechanism to realize cell membrane polarity.  ...  Ultrasensitivity, as described by Goldbeter and Koshland, has been considered for a long time as a way to realize bistable switches in biological systems.  ...  Acknowledgments GN and MS wish to thank G. Aletti, for useful discussions on mathematical modelling and numerical algorithms. Author Contributions  ... 
doi:10.1371/journal.pone.0030977 pmid:22383986 pmcid:PMC3285628 fatcat:qyihuahbqre7dkrk4wmb2wkpai
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