Here we discuss the application and articulation of biological principles for mathematical modeling of morphogenesis in the case of mammary ductal morphogenesis, with an emphasis on the default state.
Abstract
Unlike inert objects, organisms and their cells have the ability to initiate activity by themselves, and thus change their properties or states even in the absence of an external cause. This crucial difference led us to search for principles suitable for the study organisms. We propose that cells follow the default state of proliferation with variation and motility, a principle of biological inertia. This means that in the presence of sufficient nutrients, cells will express their default state. We also propose a principle of variation that addresses two central features of organisms, variation and historicity. To address interdependence between parts, we use a third principle, the principle of organization: more specifically, the notion of the closure of constraints. Within this theoretical framework, constraints are specific theoretical entities defined by their relative stability with respect to the processes they constrain. Constraints are mutually dependent in an organized system and act on the default state. <br>Here we discuss the application and articulation of these principles for mathematical modeling of morphogenesis in a specific case, that of mammary ductal morphogenesis, with an emphasis on the default state. Our model has both a biological component, the cells, and a physical component, the matrix that 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 are organized, they constrain the cells’ ability to move and to proliferate. This model exhibits a circularity that can be interpreted in terms of the closure of constraints. Implementing our mathematical model shows that constraints to the default state are sufficient to explain the formation of mammary epithelial structures. Finally, the success of this modeling effort suggests a step-wise approach whereby additional constraints imposed by the tissue and the organism can be examined in silico and rigorously tested by in vitro and in vivo experiments, in accordance with the organicist perspective we embrace.
In the last decade, the notion that new possibilities appear over time in biological phenomena has received renewed and growing attention. Kauffman approaches it as the adjacent possible, Sarti and Citti as heterogenesis, and Longo and Montévil as symmetry change and specific objects. Accordingly, there is a growing understanding that this notion is a significant shift and challenge in the way to do science. However, there has yet to be a systematic effort to bring together the different perspectives on this question in biology and in other fields confronted with it. In this conference, we intend to create bridges between the different perspectives that have been developed, mostly independently, on the question of changing possibility spaces in biology.
This Diverse Format Session will discuss some biological principles and notions that, we submit, should be integrated into the theoretical concepts of biology. Overall, these notions delineate an organism-centered biological science, by shifting the focus to the wholes rather than their parts. In particular, the session will examine how the adoption of these principles and notions fundamentally challenges the received view on biological explanation. The first notion is purposiveness. There is recent literature suggesting that biological organization can be interpreted as self-determining, and thereby intrinsically purposive (Mossio & Bich, 2017). Accepting the intrinsic purposiveness notion implies accepting a circular determination between the parts and the whole and thus a challenge to a mechanistic explanation of biological organization. The second notion is variation. In some recent studies (Montévil et al., 2016), biological variation is understood in terms of the emergence of changes that cannot be prestated. As such, biological variation challenges the very possibility of generalized formal models in biology. The third notion (Soto et al, 2016), is the biological default state according to which cells constantly grow, change shape, proliferate, and move. Because of this default state, the explanation of biological phenomena involving motility and proliferation is reversed, to the extent that what is to be accounted for is their absence (quiescence). The fourth notion is agency, which designates the capacity of organisms to behave in interaction with the environment and other organisms in a purposeful, normative, and functional way. Among other things, the conception of organisms as agents radically modifies evolutionary explanations (Jäger, 2023), insofar as agents are not only the result of selective processes, but they also actively shape selective processes. The session will consist of four short presentations (15 minutes each, maximum), followed by a discussion of 30 minutes at least, in which we will explore the capacity of these concepts to advance biological explanation, as well as their (deep) conceptual connections.
Si la physique, notamment la mécanique classique, a largement été mobilisée comme modèle de la compréhension théorique de la nature, la biologie a dans une certaine mesure, réussi à s'en détacher avec la théorie de l'évolution, une théorie où l'historicité est première. Néanmoins, cette innovation épistémologique et méthodologique n'est pas miscible avec la méthode de théorisation physique et il s'ensuit une étrange cohabitation dont les enjeux sont rarement traités. Nous proposerons des directions pour repenser la théorisation en biologie en insistant sur le concept de nouveau possible. Nous montrerons aussi que ce travail permet de mieux comprendre des phénomènes biologiques cruciaux : la disruption des organisations biologique dans l'Anthropocène.
