A Review of Mathematical Models for the Formation of\ud Vascular Networks

Mainly two mechanisms are involved in the formation of blood vasculature: vasculogenesis and angiogenesis. The former consists of the formation of a capillary-like network from either a dispersed or a monolayered population of endothelial cells, reproducible also in vitro by specific experimental assays. The latter consists of the sprouting of new vessels from an existing capillary or post-capillary venule. Similar phenomena are also involved in the formation of the lymphatic system through a process generally called lymphangiogenesis.\ud \ud A number of mathematical approaches have analysed these phenomena. This paper reviews the different modelling procedures, with a special emphasis on their ability to reproduce the biological system and to predict measured quantities which describe the overall processes. A comparison between the different methods is also made, highlighting their specific features

A self-organized model for cell-differentiation based on variations of molecular decay rates

Systemic properties of living cells are the result of molecular dynamics governed by so-called genetic regulatory networks (GRN). These networks capture all possible features of cells and are responsible for the immense levels of adaptation characteristic to living systems. At any point in time only small subsets of these networks are active. Any active subset of the GRN leads to the expression of particular sets of molecules (expression modes). The subsets of active networks change over time, leading to the observed complex dynamics of expression patterns. Understanding of this dynamics becomes increasingly important in systems biology and medicine. While the importance of transcription rates and catalytic interactions has been widely recognized in modeling genetic regulatory systems, the understanding of the role of degradation of biochemical agents (mRNA, protein) in regulatory dynamics remains limited. Recent experimental data suggests that there exists a functional relation between mRNA and protein decay rates and expression modes. In this paper we propose a model for the dynamics of successions of sequences of active subnetworks of the GRN. The model is able to reproduce key characteristics of molecular dynamics, including homeostasis, multi-stability, periodic dynamics, alternating activity, differentiability, and self-organized critical dynamics. Moreover the model allows to naturally understand the mechanism behind the relation between decay rates and expression modes. The model explains recent experimental observations that decay-rates (or turnovers) vary between differentiated tissue-classes at a general systemic level and highlights the role of intracellular decay rate control mechanisms in cell differentiation.Comment: 16 pages, 5 figure

Cardiac cell modelling: Observations from the heart of the cardiac physiome project

In this manuscript we review the state of cardiac cell modelling in the context of international initiatives such as the IUPS Physiome and Virtual Physiological Human Projects, which aim to integrate computational models across scales and physics. In particular we focus on the relationship between experimental data and model parameterisation across a range of model types and cellular physiological systems. Finally, in the context of parameter identification and model reuse within the Cardiac Physiome, we suggest some future priority areas for this field

Using mathematical models to help understand biological pattern formation

One of the characteristics of biological systems is their ability to produce and sustain spatial and spatio-temporal pattern. Elucidating the underlying mechanisms responsible for this phenomenon has been the goal of much experimental and theoretical research. This paper illustrates this area of research by presenting some of the mathematical models that have been proposed to account for pattern formation in biology and considering their implications.To cite this article: P.K. Maini, C. R. Biologies 327 (2004)

Maximizing the Adjacent Possible in Automata Chemistries

Automata chemistries are good vehicles for experimentation in open-ended evolution, but they are by necessity complex systems whose low-level properties require careful design. To aid the process of designing automata chemistries, we develop an abstract model that classifies the features of a chemistry from a physical (bottom up) perspective and from a biological (top down) perspective. There are two levels: things that can evolve, and things that cannot. We equate the evolving level with biology and the non-evolving level with physics. We design our initial organisms in the biology, so they can evolve. We design the physics to facilitate evolvable biologies. This architecture leads to a set of design principles that should be observed when creating an instantiation of the architecture. These principles are Everything Evolves, Everything’s Soft, and Everything Dies. To evaluate these ideas, we present experiments in the recently developed Stringmol automata chemistry. We examine the properties of Stringmol with respect to the principles, and so demonstrate the usefulness of the principles in designing automata chemistries

Intracellular transport driven by cytoskeletal motors: General mechanisms and defects

Cells are strongly out-of-equilibrium systems driven by continuous energy supply. They carry out many vital functions requiring active transport of various ingredients and organelles, some being small, others being large. The cytoskeleton, composed of three types of filaments, determines the shape of the cell and plays a role in cell motion. It also serves as a road network for the so-called cytoskeletal motors. These molecules can attach to a cytoskeletal filament, perform directed motion, possibly carrying along some cargo, and then detach. It is a central issue to understand how intracellular transport driven by molecular motors is regulated, in particular because its breakdown is one of the signatures of some neuronal diseases like the Alzheimer. We give a survey of the current knowledge on microtubule based intracellular transport. We first review some biological facts obtained from experiments, and present some modeling attempts based on cellular automata. We start with background knowledge on the original and variants of the TASEP (Totally Asymmetric Simple Exclusion Process), before turning to more application oriented models. After addressing microtubule based transport in general, with a focus on in vitro experiments, and on cooperative effects in the transportation of large cargos by multiple motors, we concentrate on axonal transport, because of its relevance for neuronal diseases. It is a challenge to understand how this transport is organized, given that it takes place in a confined environment and that several types of motors moving in opposite directions are involved. We review several features that could contribute to the efficiency of this transport, including the role of motor-motor interactions and of the dynamics of the underlying microtubule network. Finally, we discuss some still open questions.Comment: 74 pages, 43 figure

An Ansatz for undecidable computation in RNA-world automata

In this Ansatz we consider theoretical constructions of RNA polymers into automata, a form of computational structure. The basis for transitions in our automata are plausible RNA-world enzymes that may perform ligation or cleavage. Limited to these operations, we construct RNA automata of increasing complexity; from the Finite Automaton (RNA-FA) to the Turing Machine equivalent 2-stack PDA (RNA-2PDA) and the universal RNA-UPDA. For each automaton we show how the enzymatic reactions match the logical operations of the RNA automaton, and describe how biological exploration of the corresponding evolutionary space is facilitated by the efficient arrangement of RNA polymers into a computational structure. A critical theme of the Ansatz is the self-reference in RNA automata configurations which exploits the program-data duality but results in undecidable computation. We describe how undecidable computation is exemplified in the self-referential Liar paradox that places a boundary on a logical system, and by construction, any RNA automata. We argue that an expansion of the evolutionary space for RNA-2PDA automata can be interpreted as a hierarchical resolution of the undecidable computation by a meta-system (akin to Turing's oracle), in a continual process analogous to Turing's ordinal logics and Post's extensible recursively generated logics. On this basis, we put forward the hypothesis that the resolution of undecidable configurations in RNA-world automata represents a mechanism for novelty generation in the evolutionary space, and propose avenues for future investigation of biological automata

An information-theoretic approach to self-organisation: Emergence of complex interdependencies in coupled dynamical systems

Self-organisation lies at the core of fundamental but still unresolved scientific questions, and holds the promise of de-centralised paradigms crucial for future technological developments. While self-organising processes have been traditionally explained by the tendency of dynamical systems to evolve towards specific configurations, or attractors, we see self-organisation as a consequence of the interdependencies that those attractors induce. Building on this intuition, in this work we develop a theoretical framework for understanding and quantifying self-organisation based on coupled dynamical systems and multivariate information theory. We propose a metric of global structural strength that identifies when self-organisation appears, and a multi-layered decomposition that explains the emergent structure in terms of redundant and synergistic interdependencies. We illustrate our framework on elementary cellular automata, showing how it can detect and characterise the emergence of complex structures