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Register a new userA model for the self-organization of vesicular flux and protein distributions in the Golgi apparatus
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The generation of two non-identical membrane compartments via exchange of vesicles is considered to require two types of vesicles specified by distinct cytosolic coats that selectively recruit cargo and two membrane-bound SNARE pairs that specify fusion and differ in their affinities for each type of vesicles. The mammalian Golgi complex is composed of 6-8 non-identical cisternae that undergo gradual maturation and replacement yet features only two SNARE pairs. We present a model that explains how the distinct composition of Golgi cisternae can be generated with two and even a single SNARE pair and one vesicle coat. A decay of active SNARE concentration in aging cisternae provides the seed for a cis > trans SNARE gradient that generates the predominantly retrograde vesicle flux which further enhances the gradient. This flux in turn yields the observed inhomogeneous steady-state distribution of Golgi enzymes, which compete with each other and with the SNAREs for incorporation into transport vesicles. We show analytically that the steady state SNARE concentration decays exponentially with the cisterna number. Numerical solutions of rate equations reproduce the experimentally observed SNARE gradients, overlapping enzyme peaks in cis, medial and trans and the reported change in vesicle nature across Golgi: Vesicles originating from younger cisternae mostly contain Golgi enzymes and SNAREs enriched in these cisternae and extensively recycle through the Endoplasmic Reticulum (ER), while the other subpopulation of vesicles contains Golgi proteins prevalent in older cisternae and hardly reaches the ER.
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The network concept is increasingly used for the description of complex systems. Here we summarize key aspects of the evolvability and robustness of the hierarchical network-set of macromolecules, cells, organisms, and ecosystems. Listing the costs and benefits of cooperation as a necessary behaviour to build this network hierarchy, we outline the major hypothesis of the paper: the emergence of hierarchical complexity needs cooperation leading to the ageing (i.e. gradual deterioration) of the constituent networks. A stable environment develops cooperation leading to over-optimization, and forming an always-old network, which accumulates damage, and dies in an apoptosis-like process. A rapidly changing environment develops competition forming a forever-young network, which may suffer an occasional over-perturbation exhausting system-resources, and causing death in a necrosis-like process. Giving a number of examples we demonstrate how cooperation evokes the gradual accumulation of damage typical to ageing. Finally, we show how various forms of cooperation and consequent ageing emerge as key elements in all major steps of evolution from the formation of protocells to the establishment of the globalized, modern human society.
Circadian clocks play a pivotal role in orchestrating numerous physiological and developmental events. Waveform shapes of the oscillations of protein abundances can be informative about the underlying biochemical processes of circadian clocks. We derive a mathematical framework where waveforms do reveal hidden biochemical mechanisms of circadian timekeeping. We find that the cost of synthesizing proteins with particular waveforms can be substantially reduced by rhythmic protein half-lives over time, as supported by previous plant and mammalian data, as well as our own seedling experiment. We also find that previously-enigmatic, cyclic expression of positive arm components within the mammalian and insect clocks allows both a broad range of peak time differences between protein waveforms and the symmetries of the waveforms about the peak times. Such various peak-time differences may facilitate tissue-specific or developmental stage-specific multicellular processes. Our waveform-guided approach can be extended to various biological oscillators, including cell-cycle and synthetic genetic oscillators.
Scale-free outbursts of activity are commonly observed in physical, geological, and biological systems. The idea of self-organized criticality (SOC), introduced back in 1987 by Bak, Tang and Wiesenfeld suggests that, under certain circumstances, natural systems can seemingly self-tune to a critical state with its concomitant power-laws and scaling. Theoretical progress allowed for a rationalization of how SOC works by relating its critical properties to those of a standard non-equilibrium second-order phase transition that separates an active state in which dynamical activity reverberates indefinitely, from an absorbing or quiescent state where activity eventually ceases. Here, we briefly review these ideas as well as a recent closely-related concept: self-organized bistability (SOB). In SOB, the very same type of feedback operates in a system characterized by a discontinuos phase transition, which has no critical point but instead presents bistability between active and quiescent states. SOB also leads to scale-invariant avalanches of activity but, in this case, with a different type of scaling and coexisting with anomalously large outbursts. Moreover, SOB explains experiments with real sandpiles more closely than SOC. We review similarities and differences between SOC and SOB by presenting and analyzing them under a common theoretical framework, covering recent results as well as possible future developments. We also discuss other related concepts for imperfect self-organization such as self-organized quasi-criticality and self-organized collective oscillations, of relevance in e.g. neuroscience, with the aim of providing an overview of feedback mechanisms for self-organization to the edge of a phase transition.
We introduce a minimal Agent Based Model with two classes of agents, fundamentalists (stabilizing) and chartists (destabilizing) and we focus on the essential features which can generate the stylized facts. This leads to a detailed understanding of the origin of fat tails and volatility clustering and we propose a mechanism for the self-organization of the market dynamics in the quasi-critical state. The stylized facts are shown to correspond to finite size effects which, however, can be active at different time scales. This implies that universality cannot be expected in describing these properties in terms of effective critical exponents. The introduction of a threshold in the agents action (small price fluctuations lead to no-action) triggers the self-organization towards the quasi-critical state. Non-stationarity in the number of active agents and in their action plays a fundamental role. The model can be easily generalized to more realistic variants in a systematic way.
Long cell protrusions, which are effectively one-dimensional, are highly dynamic subcellular structures. Length of many such protrusions keep fluctuating about the mean value even in the the steady state. We develop here a stochastic model motivated by length fluctuations of a type of appendage of an eukaryotic cell called flagellum (also called cilium). Exploiting the techniques developed for the calculation of level-crossing statistics of random excursions of stochastic process, we have derived analytical expressions of passage times for hitting various thresholds, sojourn times of random excursions beyond the threshold and the extreme lengths attained during the lifetime of these model flagella. We identify different parameter regimes of this model flagellum that mimic those of the wildtype and mutants of a well known flagellated cell. By analysing our model in these different parameter regimes, we demonstrate how mutation can alter the level-crossing statistics even when the steady state length remains unaffected by the same mutation. Comparison of the theoretically predicted level crossing statistics, in addition to mean and variance of the length, in the steady state with the corresponding experimental data can be used in near future as stringent tests for the validity of the models of flagellar length control. The experimental data required for this purpose, though never reported till now, can be collected, in principle, using a method developed very recently for flagellar length fluctuations.
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