Bulletin of the American Physical Society
APS March Meeting 2014
Volume 59, Number 1
Monday–Friday, March 3–7, 2014; Denver, Colorado
Session J15: Focus Session: Phase Transitions and Criticality in Cells |
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Sponsoring Units: DBIO Chair: Chase Broedersz, Princeton University Room: 304 |
Tuesday, March 4, 2014 2:30PM - 3:06PM |
J15.00001: Physical limits of cells and proteomes Invited Speaker: Ken Dill The biomass in cells is mostly protein. So, it is natural to expect that some of the physical behaviors of cells, including components of their growth laws, should be explainable in terms of the physical properties of cellular proteomes, the sum total of a cells proteins. We develop simple physical models for how cells respond to temperature, osmotic pressure, and under different growth conditions. [Preview Abstract] |
Tuesday, March 4, 2014 3:06PM - 3:18PM |
J15.00002: Stochasticity and universal dynamics in communicating cellular populations Javad Noorbakhsh, Pankaj Mehta A fundamental problem in biology is to understand how biochemical networks within individual cells coordinate and control population-level behaviors. Our knowledge of these biochemical networks is often incomplete, with little known about the underlying kinetic parameters. Here, we present a general modeling approach for overcoming these challenges based on universality. We apply our approach to study the emergence of collective oscillations of the signaling molecule cAMP in populations of the social amoebae \textit{Dictyostelium discoideum} and show that a simple two-dimensional dynamical system can reproduce signaling dynamics of single cells and successfully predict novel population-level behaviors. We reduce all the important parameters of our model to only two and will study its behavior through a phase diagram. This phase diagram determines conditions under which cells are quiet or oscillating either coherently or incoherently. Furthermore it allows us to study the effect of different model components such as stochasticity, multicellularity and signal preprocessing. A central finding of our model is that \textit{Dictyostelium} exploit stochasticity within biochemical networks to control population level behaviors. [Preview Abstract] |
Tuesday, March 4, 2014 3:18PM - 3:30PM |
J15.00003: Morphogenesis at criticality? Dmitry Krotov, Julien Dubuis, Thomas Gregor, William Bialek Spatial patterns in the early fruit fly embryo emerge from a network of interactions among transcription factors, the gap genes, driven by maternal inputs. Such networks can exhibit many qualitatively different behaviors, separated by critical surfaces. At criticality, we should observe strong correlations in the fluctuations of different genes around their mean expression levels, a slowing of the dynamics along some but not all directions in the space of possible expression levels, correlations of expression fluctuations over long distances in the embryo, and departures from a Gaussian distribution of these fluctuations. Analysis of recent experiments on the gap genes shows that all these signatures are observed, and that the different signatures are related in ways predicted by theory. While there might be other explanations for these individual phenomena, the confluence of evidence suggests that this genetic network is tuned to criticality. [Preview Abstract] |
Tuesday, March 4, 2014 3:30PM - 3:42PM |
J15.00004: Cell-cell interactions stabilize emerging collective migration modes Joshua Parker, Can Guven, Chenlu Wang, Ed Ott, Wolfgang Losert We propose a coarse-grained mechanistic model for simulating the dynamics of the biological model organism \textit{Dictyostelium discoideum}, incorporating gradient sensing, random motility via actin protrusions, persistent random motion and signal relay. We demonstrate that our simple cell model does result in the macroscopic group migration patterns seen in no-flow gradient chambers, namely a transition from individual motion to multi-cell ``streaming'' to aggregation as the external signal is decreased. We also find that cell-cell adhesion further stabilizes the contact network independent of chemical signaling, suggesting no indirect feedback between mechanical forces and gradient sensing. We discuss further modifications to the model and as well as further applications to quantifying dynamics using spatio-temporal contact networks. [Preview Abstract] |
Tuesday, March 4, 2014 3:42PM - 3:54PM |
J15.00005: Emergence of Critical Behavior in $\beta $-Cell Network Matthew Westacott, Thomas Hraha, Mason Mcclatchey, Marina Pozzoli, Richard Benninger The $\beta $-cell is a cell type located in the Islet of Langerhans, a micro-organ of the pancreas which maintains glucose homeostasis through secretion of insulin. An electrophysiological process governing insulin release occurs through initial uptake of blood glucose and generation of ATP which inhibits the ATP sensitive potassium channel (K-ATP) causing membrane depolarization (activation). Neighboring $\beta $-cells are electrically coupled through gap junctions which allow passage of cationic molecules, creating a network of coupled electrical oscillators. Cells exhibiting hyperpolzarized (inactive) membrane potential affect behavior of neighboring cells by electrically suppressing their depolarization. Here we observe critical behavior between global active-inactive states by increasing the number of inactive elements with the K-ATP inhibitor Diazoxide and a tunable ATP insensitive transgenic mouse model. We show this behavior occurs due to from cell-cell coupling as mice lacking $\beta $-cell gap junctions show no critical behavior. Also, a computational $\beta $-cell model was expanded to construct a coupled $\beta $-cell network and we show this model replicates the critical behavior seen \textit{in-vitro. }While electrical activity of single $\beta $-cells is well studied these data highlight a newly defined characteristic of their emergent multicellular behavior within the Islet of Langerhans and may elucidate pathophysiology of Diabetes due to mutations in the K-ATP channel. [Preview Abstract] |
Tuesday, March 4, 2014 3:54PM - 4:06PM |
J15.00006: Phase transition in Caenorhabditis elegans: A classical oil-water phase separation? Christoph Weber In Caenorhabditis elegans droplets form before the cell divides. These droplets, also referred to as P-granules, consist of a variety of unstructured proteins and mRNA. Brangwynne et al. [Science, 2009] showed that the P-granules exhibit fluid-like behavior and that the phase separation is controlled spatially by a gradient of a component called Mex-5. It is believed that this system exhibits the same characteristics as a classical oil-water phase separation. Here we report the recent experimental investigations on the phase separation in Caenorhabditis elegans and compare our findings with a classical oil-water phase separation. Specifically, we consider the underlying coarsening mechanisms as well as the impact of temperature and species composition. Finally, we present a preliminary model incorporating the characteristics of the phase separation kinetics for Caenorhabditis elegans. [Preview Abstract] |
Tuesday, March 4, 2014 4:06PM - 4:18PM |
J15.00007: Anesthetics lower $T_c$ of a 2D miscibility critical point in the plasma membrane Benjamin Machta, Elly Gray, Sarah Veatch Many small hydrophobic molecules induce general anesthesia. Their efficacy as anesthetics has been shown to correlate both with their hydrophobicity and with their potency in inhibiting certain ligand gated ion channels. I will first report on our experiments on the effects that these molecules have on the two-dimensional miscibility critical point observed in cell derived vesicles (GPMVs). We show that anesthetics depress the critical temperature ($T_c$) of these GPMVs but do not strongly affect the ratio of phases found below $T_c$. The magnitude of this affect is consistent across the n-alcohols only when their concentration is rescaled by the median anesthetic concentration (AC50) for tadpole anesthesia and at AC50 we see a 4K downward shift in $T_c$. I will next present a model in which anesthetics interfere with native allosteric regulation of ligand gated channels by the critical membrane, showing that our observed change in critical properties could lead to the previously observed changes in channel conductance without a direct interaction between anesthetic molecules and their target proteins. Finally, I will discuss ongoing experiments that will clarify the role of this membrane effect in mediating the organism level anesthetic response. [Preview Abstract] |
Tuesday, March 4, 2014 4:18PM - 4:30PM |
J15.00008: A Hessian geometric construction that aids analysis of non-monotonic effects in ternary mixture phase separation George Thurston, Douglas Hayden, David Ross, Ajay Pande, Jayanti Pande, Giuseppe Foffi, Anna Stradner, Peter Schurtenberger Ternary, quaternary, and multi-component phase separations are common in biological systems, and their properties have many physiological and pathological consequences. As one example, understanding the molecular origins of the phase boundaries of eye lens protein solutions can help understand loss of transparency of the eye lens in cataract, a leading cause of blindness. The phase boundaries respond in a sensitive and non-monotonic fashion to small changes in molecular interaction strengths. We show how the geometry of relevant intersections, in the space of the components of the Hessian of the intensive Gibbs free energy with respect to relative compositions, can assist in comprehending the origins of such non-monotonic and sensitive changes of the phase boundaries. We apply this construction to analyze recent results about non-monotonic dependence of the phase boundaries of eye lens protein solutions on interprotein interaction strengths. [Preview Abstract] |
Tuesday, March 4, 2014 4:30PM - 4:42PM |
J15.00009: The geometry of the Waddington Landscape Ling-Nan Zou, Adele Doyle, Sumin Jang, Sharad Ramanathan We study the ``landscape'' of cell states that emerge during \textit{in vitro} differentiation of mouse embryonic stem (ES) cells. Profiling the gene expression of cell populations captured at specific locations along different developmental trajectories, we uncover a low-dimensional landscape with an ultrametric distance structure between states; this provide a natural basis (and limit) for reconstructing cell lineages from gene expression profiles. From the correlation spectrum of this landscape, we infer ``directions'' in gene expression along which cells transition from one state to another, as well as signaling pathways that control these transitions. Finally, we study the dynamics of cell movement on this landscape using an ES cell line where yellow fluorescent protein (YFP) has been fused to Otx2, a transcription factor that plays an important role during early development. [Preview Abstract] |
Tuesday, March 4, 2014 4:42PM - 5:18PM |
J15.00010: Finite size effects in subnuclear RNA/protein phase transitions Invited Speaker: Cliff Brangwynne |
Tuesday, March 4, 2014 5:18PM - 5:30PM |
J15.00011: Zipf's law and criticality in multivariate data without fine-tuning David Schwab, Ilya Nemenman, Pankaj Mehta Recently it has become possible to directly measure simultaneous collective states of many biological components, such as neural activities or antibody sequences. A striking result has been the observation that the underlying probability distributions of the collective states of these systems exhibit a feature known as Zipf's law. They appear poised near a unique critical point, where the extensive parts of the entropy and energy exactly cancel. Here we present analytical arguments and numerical simulations showing that such behavior naturally arises in systems with an unobserved random variable (e.g., input stimulus to a neural system) that affects the observed data. The mechanism does not require fine tuning and may help explain the ubiquity of Zipf's law in disparate systems. [Preview Abstract] |
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