Résumé:

One important role which the cytoskeleton plays in cells is to provide a network of filaments along which molecular motors can procede. This provides an essential mechanism by which a cell can establish transport of cargos over distances of the order of the cell size. The details of how such motors achieve procession along the biofilaments constituting the cytoskeleton are very complex indeed, but much of their behaviour (including collective aspects of the transport) can be described in terms of well-established models, such as the Totally Asymmetric Transport Process (TASEP) or similar. These are well-studied on single filaments. Recent work has allowed us to establish a framework to transpose this understanding to an overall network of interconnected filaments, mimicking the cytoskeleton. We discuss how new aspects of heterogeneity arise on the network scale, and we aOne important role which the cytoskeleton plays in cells is to provide a network of filaments along which molecular motors can procede. This provides an essential mechanism by which a cell can establish transport of cargos over distances of the order of the cell size. The details of how such motors achieve procession along the biofilaments constituting the cytoskeleton are very complex indeed, but much of their behaviour (including collective aspects of the transport) can be described in terms of well-established models, such as the Totally Asymmetric Transport Process (TASEP) or similar. These are well-studied on single filaments. Recent work has allowed us to establish a framework to transpose this understanding to an overall network of interconnected filaments, mimicking the cytoskeleton. We discuss how new aspects of heterogeneity arise on the network scale, and we argue that they are generic to many types of transport on networks. We also present very recent ideas for incorporating more complex features aimed at applying the approach to cytoskeletal transport in particular. rgue that they are generic to many types of transport on networks. We also present very recent ideas for incorporating more complex features aimed at applying the approach to cytoskeletal transport in particular.

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At University Montpellier 2, the modeling and simulation of complex systems has been identified as a major scientific challenge and one of the priority axes in interdisciplinary research, with major potential impact on training, economy and society. Many research groups and laboratories in Montpellier are already working in that direction, but typically in isolation within their own scientific discipline. Several local actions have been initiated in order to structure the scientific community with interdisciplinary projects, but with little coordination among the actions. The goal of the ModSysC2020 (modeling and simulation of complex systems in 2020) working group was to analyze the local situation (forces and weaknesses, current projects), identify the critical research directions and propose concrete actions in terms of research projects, equipment facilities, human resources and training to be encouraged. To guide this perspective, we decomposed the scientific challenge into four main themes, for which there is strong background in Montpellier: (1) modeling and simulation of complex systems; (2) algorithms and computing; (3) scientific data management; (4) production, storage and archiving of data from the observation of the natural and biological media. In this report, for each theme, we introduce the context and motivations, analyze the situation in Montpellier, identify research directions and propose specific actions in terms of interdisciplinary research projects and training. We also provide an analysis of the socio-economical aspects of modeling and simulation through use cases in various domains such as life science and healthcare, environmental science and energy. Finally, we discuss the importance of revisiting students training in fundamental domains such as modeling, computer programming and database which are typically taught too late, in specialized masters.

Commentaires: Final Report of the ModSysC2020 Working Group at University Montpellier 2

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Tubular lipid membranes (TLMs) are nanoscopic cylindrical assemblies that play a fundamental role in many intracellular and intercellular processes like protein trafficking, signaling and organelle morphogenesis. TLMs are generated by different mechanochemical actions, ranging from mechanical forces produced by motor proteins pulling at one TLM-end up to specific chemical activities of membrane-associated proteins. We develop here a theory of a resonant effect in protein-membrane coupling taking place in the vicinity of instabilities in tubular lipid membranes (TLMs) under longitudinal force and pressure difference constraints. Two critical low-energy modes defining the stability domain boundaries are found. We show that these modes mediate long-range TLM-protein coupling and interactions between absorbed proteins. Besides, TLM mechanical instabilities strongly influence protein desorption and protein cluster nucleation on TLMs. Experiments involving nanomechanical devices extracting TLM over a large spectrum of mechanochemical conditions can directly test model predictions.

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DOI: 10.1103/PhysRevLett.107.068702
WoS: 000293562900005
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78 Citations
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We study the totally asymmetric simple exclusion process (TASEP) on complex networks, as a paradigmatic model for transport subject to excluded volume interactions. Building on TASEP phenomenology on a single segment and borrowing ideas from random networks we investigate the effect of connectivity on transport. In particular, we argue that the presence of disorder in the topology of vertices crucially modifies the transport features of a network: irregular networks involve homogeneous segments and have a bimodal distribution of edge densities, whereas regular networks are dominated by shocks leading to a unimodal density distribution. The proposed numerical approach of solving for mean-field transport on networks provides a general framework for studying TASEP on large networks, and is expected to generalize to other transport processes.

Commentaires: arXiv:1105.2905v2; see also highlight in Physical Review Focus http://focus.aps.org/story/v28/st6

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PMID 20867743
DOI: 10.1103/PhysRevLett.105.028102
WoS: 000279653500001
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11 Citations
Résumé:

We develop a theory of a resonant effect in protein-membrane coupling taking place in the vicinity of instabilities in tubular lipid membranes (TLMs) under longitudinal force and pressure difference constraints. Two critical low-energy modes defining the stability domain boundaries are found. We show that these modes mediate long-range TLM-protein coupling and interactions between absorbed proteins. Besides, TLM mechanical instabilities strongly influence protein desorption and protein cluster nucleation on TLMs. Model predictions can be tested over a large spectrum of mechanochemical conditions

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DOI: 10.1007/978-3-540-77074-9_75
WoS: 000268634700075
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5 Citations
Résumé:

Intracellular motion driven by motor proteins on cytoskeletal filaments provides an interesting example for studying non-equilibrium transport phenomena. We will discuss a 3-dimensional lattice gas model, based on the generalization of a totally asymmetric exclusion process with non conserved dynamics (TASEP coupled with Langmuir Kinetics). In particular, we will focus on emergent physical properties, specific to the three-dimensional geometry, concerning traffic jam and phase separation phenomena, with interesting biological implications for real intracellular transport processes.