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  1. Theoretical approach of ductal morphogenesis

    Theoretical approach of ductal morphogenesis

    Journal of Theoretical and Applied Vascular Research


    We propose a theoretical framework to model the behavior of cells in tissues and develop an application in the case of duct morphogenesis in mammary glands.

    Abstract

    We developed 3D culture methods that reproduce in vitro mammary gland ductal morphogenesis. We are proposing a conceptual framework to understand morphogenetic events based on epistemologically sound biological principles instead of the common practice of using only physical principles. More specifically, our theoretical framework is based on the principle that the default state of cells is proliferation with variation and motility. We emphasize the role played by the agency of cells embedded in a gel and the circularity that is relevant for the intended process, whereby cells act upon other cells and on matrix elements, and are subject to the agentivity of neighboring cells. This circularity strongly differs from classical linear causality. Finally, our approach opens up the study of causal determination to multilevel explanations rather than to reductive ones involving only molecules in general and genes in particular.

    Keywords: Morphogenesis, extracellular matrix, theoretical principles, default state of cells, modelization.

    Citation
    Montevil, M., Carlos Sonnenschein, and Ana M. Soto. 2016. “Theoretical Approach of Ductal Morphogenesis.” Journal of Theoretical and Applied Vascular Research 1 (1): 45–49. https://doi.org/10.24019/jtavr.7
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  2. Modeling mammary gland from biological first principles.


    We strudy 3D culture methods that reproduce in vitro mammary gland ductal morphogenesis. We are proposing a conceptual framework to understand morphogenetic events based on epistemologically sound biological principles instead of using only physical principles. More specifically, our theoretical framework is based on the principle that the default state of cells is proliferation with variation and motility. We emphasize the role played by the agency of cells embedded in a gel and the circularity that is relevant for the intended process, whereby cells act upon other cells and on matrix elements, and are subject to the agency of neighboring cells. This circularity strongly differs from classical linear causality. Finally, our approach opens up the study of causal determination to multilevel explanations rather than to reductive ones involving only molecules in general and genes in particular.

  3. From the century of the genome to the century of the organism: New theoretical approaches

    From the century of the genome to the century of the organism: New theoretical approaches

    Progress in Biophysics and Molecular Biology, Special issue


    This focused issue of Progress in Biophysics and Molecular Biology is entitled "From the century of the genome to the century of the organism: New theoretical approaches." It was developed during Ana M. Soto’s tenure as Blaise Pascal Chair of Biology 2013-15 at the Ecole Normale Supérieure (ENS,...

    Abstract

    This focused issue of Progress in Biophysics and Molecular Biology is entitled "From the century of the genome to the century of the organism: New theoretical approaches." It was developed during Ana M. Soto’s tenure as Blaise Pascal Chair of Biology 2013-15 at the Ecole Normale Supérieure (ENS, Paris, France). Giuseppe Longo was the Pascal Chair host at the ENS. This ongoing theoretical was also used as the content of a 10 session course attended by graduate students and post-graduates, which took place at the National Museum of Natural History and at the ENS. The attendants of course encouraged the guest editors to make this material easily available, hence the origin of PBMB issue.

    Citation
    Soto, Ana M., G. Longo, Denis Noble, Nicole Perret, Maël Montévil, Carlos Sonnenschein, Matteo Mossio, Arnaud Pocheville, Paul-Antoine Miquel, and Su-Young Hwang. 2016. “From the Century of the Genome to the Century of the Organism: New Theoretical Approaches.” Progress in Biophysics and Molecular Biology, Special Issue 122 (1): 1–82. https://www.sciencedirect.com/journal/progress-in-biophysics-and-molecular-biology/vol/122/issue/1
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  4. Modeling mammary organogenesis from biological first principles: Cells and their physical constraints

    Modeling mammary organogenesis from biological first principles: Cells and their physical constraints

    Progress in Biophysics and Molecular Biology


    We developed a mathematical model of mammary gland based on proper biological principles: the default state of cells and the principle of organization.

    Abstract

    Abstract In multicellular organisms, relations among parts and between parts and the whole are contextual and interdependent. These organisms and their cells are ontogenetically linked: an organism starts as a cell that divides producing non-identical cells, which organize in tri-dimensional patterns. These association patterns and cells types change as tissues and organs are formed. This contextuality and circularity makes it difficult to establish detailed cause and effect relationships. Here we propose an approach to overcome these intrinsic difficulties by combining the use of two models; 1) an experimental one that employs 3D culture technology to obtain the structures of the mammary gland, namely, ducts and acini, and 2) a mathematical model based on biological principles. The typical approach for mathematical modeling in biology is to apply mathematical tools and concepts developed originally in physics or computer sciences. Instead, we propose to construct a mathematical model based on proper biological principles. Specifically, we use principles identified as fundamental for the elaboration of a theory of organisms, namely i) the default state of cell proliferation with variation and motility and ii) the principle of organization by closure of constraints. This model has a biological component, the cells, and a physical component, a matrix which contains collagen fibers. Cells display agency and move and proliferate unless constrained; they exert mechanical forces that i) act on collagen fibers and ii) on other cells. As fibers organize, they constrain the cells on their ability to move and to proliferate. The model exhibits a circularity that can be interpreted in terms of closure of constraints. Implementing the mathematical model shows that constraints to the default state are sufficient to explain ductal and acinar formation, and points to a target of future research, namely, to inhibitors of cell proliferation and motility generated by the epithelial cells. The success of this model suggests a step-wise approach whereby additional constraints imposed by the tissue and the organism could be examined in silico and rigorously tested by in vitro and in vivo experiments, in accordance with the organicist perspective we embrace.

    Keywords: Ductal morphogenesis, Mathematical models, Organicism, Organizational closure, Acinar morphogenesis, Mammary gland morphogenesis

    Citation
    Montévil, Maël, L. Speroni, Carlos Sonnenschein, and Ana M. Soto. 2016. “Modeling Mammary Organogenesis from Biological First Principles: Cells and Their Physical Constraints.” Progress in Biophysics and Molecular Biology 122 (1): 58–69. https://doi.org/10.1016/j.pbiomolbio.2016.08.004
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  5. Theoretical principles for biology: Variation

    Theoretical principles for biology: Variation

    Progress in Biophysics and Molecular Biology


    Biological variation should be given the status of a fundamental theoretical principle in biology. Variation goes with randomness, historicity and contextuality.

    Abstract

    Abstract Darwin introduced the concept that random variation generates new living forms. In this paper, we elaborate on Darwin’s notion of random variation to propose that biological variation should be given the status of a fundamental theoretical principle in biology. We state that biological objects such as organisms are specific objects. Specific objects are special in that they are qualitatively different from each other. They can undergo unpredictable qualitative changes, some of which are not defined before they happen. We express the principle of variation in terms of symmetry changes, where symmetries underlie the theoretical determination of the object. We contrast the biological situation with the physical situation, where objects are generic (that is, different objects can be assumed to be identical) and evolve in well-defined state spaces. We derive several implications of the principle of variation, in particular, biological objects show randomness, historicity and contextuality. We elaborate on the articulation between this principle and the two other principles proposed in this special issue: the principle of default state and the principle of organization.

    Keywords: Variability, Historicity, Genericity, Biological randomness, Organization, Theory of organisms

    Citation
    Montévil, Maël, Matteo Mossio, A. Pocheville, and G. Longo. 2016. “Theoretical Principles for Biology: Variation.” Progress in Biophysics and Molecular Biology 122 (1): 36–50. https://doi.org/10.1016/j.pbiomolbio.2016.08.005
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  6. Theoretical principles for biology: Organization

    Theoretical principles for biology: Organization

    Progress in Biophysics and Molecular Biology


    In the search of a theory of biological organisms, we propose to adopt organization as a theoretical principle and define it as closure of constraints.

    Abstract

    Abstract In the search of a theory of biological organisms, we propose to adopt organization as a theoretical principle. Organization constitutes an overarching hypothesis that frames the intelligibility of biological objects, by characterizing their relevant aspects. After a succinct historical survey on the understanding of organization in the organicist tradition, we offer a specific characterization in terms of closure of constraints. We then discuss some implications of the adoption of organization as a principle and, in particular, we focus on how it fosters an original approach to biological stability, as well as and its interplay with variation.

    Keywords: Theoretical principle, Organization, Constraints, Closure, Stability, Organicism

    Citation
    Mossio, Matteo, Maël Montévil, and G. Longo. 2016. “Theoretical Principles for Biology: Organization.” Progress in Biophysics and Molecular Biology 122 (1): 24–35. https://doi.org/10.1016/j.pbiomolbio.2016.07.005
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  7. Toward a theory of organisms: Three founding principles in search of a useful integration

    Toward a theory of organisms: Three founding principles in search of a useful integration

    Progress in Biophysics and Molecular Biology


    We articulate three principles for a theory of organisms proposed, namely: the default state the principle of variation and the principle of organization.

    Abstract

    Abstract Organisms, be they uni- or multi-cellular, are agents capable of creating their own norms; they are continuously harmonizing their ability to create novelty and stability, that is, they combine plasticity with robustness. Here we articulate the three principles for a theory of organisms, namely: the default state of proliferation with variation and motility, the principle of variation and the principle of organization. These principles profoundly change both biological observables and their determination with respect to the theoretical framework of physical theories. This radical change opens up the possibility of anchoring mathematical modeling in biologically proper principles.

    Keywords: Default state, Biological organization, Organizational closure, Variation, Individuation

    Citation
    Soto, Ana M., G. Longo, P.-A. Miquel, M. Montevil, Matteo Mossio, N. Perret, A. Pocheville, and Carlos Sonnenschein. 2016. “Toward a Theory of Organisms: Three Founding Principles in Search of a Useful Integration.” Progress in Biophysics and Molecular Biology 122 (1): 77–82. https://doi.org/10.1016/j.pbiomolbio.2016.07.006
    Manuscript Citation Publisher Full text
  8. Modeling mammary organogenesis from biological first principles: cells and their physical constraints


    We have proposed the following principles for the elaboration of a theory of organisms: i) the default state of cell proliferation with variation and motility and b) the principle of organization by closure of constraints. We now propose to use them to frame experiments using experimental biological models and mathematical modeling. The typical way of doing mathematical modeling in biology is to apply mathematical tools and concepts developed originally in physics. Instead, we propose to use the biological principles mentioned above as bases for our modeling effort. This model has a biological component, the cells, and a physical component, a matrix which contains collagen fibers. Cells are agents that move and proliferate unless constrained; they exert mechanical forces that i) act on collagen fibers and ii) on other cells. As fibers get organized, they constrain the cells on their ability to move and to proliferate. The model exhibits a circularity that can be interpreted in terms of closure of constraints. Implementing the mathematical model shows that constraints to the default state are sufficient to explain ductal and acinar formation, and points to a target of future research, namely, to inhibitors of cell proliferation and motility generated by the epithelial cells. The success of this model suggests a step-wise approach whereby additional constraints imposed by the tissue and the organism could be examined in silico and rigorously tested by in vitro and in vivo experiments, in accordance with the organicist perspective we embrace.

  9. The biological default state of cell proliferation with variation and motility, a fundamental principle for a theory of organisms

    The biological default state of cell proliferation with variation and motility, a fundamental principle for a theory of organisms

    Progress in Biophysics and Molecular Biology


    We propose a biological default state of proliferation with variation and motility by analogy with physics inertia. Then, quiescence requires an explanation.

    Abstract

    Abstract The principle of inertia is central to the modern scientific revolution. By postulating this principle Galileo at once identified a pertinent physical observable (momentum) and a conservation law (momentum conservation). He then could scientifically analyze what modifies inertial movement: gravitation and friction. Inertia, the default state in mechanics, represented a major theoretical commitment: there is no need to explain uniform rectilinear motion, rather, there is a need to explain departures from it. By analogy, we propose a biological default state of proliferation with variation and motility. From this theoretical commitment, what requires explanation is proliferative quiescence, lack of variation, lack of movement. That proliferation is the default state is axiomatic for biologists studying unicellular organisms. Moreover, it is implied in Darwin’s “descent with modification”. Although a “default state” is a theoretical construct and a limit case that does not need to be instantiated, conditions that closely resemble unrestrained cell proliferation are readily obtained experimentally. We will illustrate theoretical and experimental consequences of applying and of ignoring this principle.

    Keywords: Default state, Theory, Organicism, Emergence, Mathematical symmetries, Biological organization

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