developed by Ed Munro, Kristin Sherrard, Eliana Hechter and Adriana Dawes
Morphogenie is a flexible software tool designed to explore how morphogenetic dynamics of single cells and multicellular tissues emerge from a local interplay between biochemical kinetics and cytoskletal mechanics. In Morphogenie, cells are built from a collection of many discrete elements or agents, which come in two basic types.
Macroscopic agents represent macroscopic parts of cells - e.g. a piece of the cell cortex or internal cytoplasm or the nucleus. These act simultaneously as mechanical entities and chemical compartments. As a mechanical entity, each is endowed distinct active (e.g. contractile) and passive (viscolastic) properties designed to mimic those known or hypothesized for their biological counterparts. Newton's Laws govern how the moment to moment exchange of forces between neighboring elements lead deformation and movement of those elements and thus to changes in cell shape and porganization. At the same time kinetic rules govern the local production, conversion and loss of different factors within each compartment and govern their local exchange, by diffusion or otherwise, between neighboring compartments. The coupling betwen mechanics and biochemistry comes (a) from the fact that as macroscopic elements move and deform, they transport and concentrate or rarify the factors they contain; and (b) from a hypothesized dependence of mechanical properties of each element on the local concentrations of factors it contains.
Microscopic agents represent individual molecules or molecular complexes (e.g. adhesion proteins) that reside within specific macroscopic compartments and whose dynamics are governed by local force balance and a stochastic representation of biochemical kinetics.
Like our gene network simulator Ingeneue, Morphogie allows a user to flexibly specify and configure a network of biochemical interactions and then automatically distributes computation of the resulting dynamics across many sub-cellular compartments (by numerically solving the large system of ODEs these interactions and the compartmental geometry imply) . Unlike Ingeneue, which only operates on a fixed grid of cells, Morphogenie accomodates arbitrary geometries, an arbitrary and ever-changing number of subcellular compartments and correctly preserves the conservation of "stuff" as compartments move and deform and as factors flux between compartments with different volumes.
In an analogous fashion, Morphogenie allows a user to flexibly configure the "rules" which govern the constitutive mechanical properties of macroscopic and microscopic elements and to specify how these depend on the concentrations of factors within macroscopic elements or the biochemcial state of microscopic elements. Morphogenie then automatically constructs and solves the large system of ODE force balance equations that govern the moment-to-moment movements and deformations of all elements.
At present, Morphogenie runs in one of two modes from text-file input that specifies the network of biochemical interactions, mechanical properties of subcellular parts, composition of individual cells and initial disposition of cells within multicellular tissues, values of parameters that govern local mechanics and biochemistry, etc. In the first mode, a graphical user interface allows the user to load files, run simulations, modify parameters and initial conditions, display simulation results via a simple "movie player", and export the results as individual movie frames. In a second mode, the user can configure and then run parameter space searches as distributed computations across a large cluster of individual computers, storing the results on disk, and then use the GUI to display and evaluate the results.
Morphogenie is a work in progress, developed in the context of our ongoing research. We have exploited object-oriented approaches to design a core framework that is both robust and highly flexible, which can be extended to tackle new research problems through the addition of new code modules without the necessity to redesign the entire framework. We are now busily adding such modules ourselves. As soon as our first paper using Morphogenie is published, we plan to make the code available as open source with documentation that will allow others to use and extend Morphogenie under a standard GNU licence. Click here to view a tutorial on simulating morphogenesis in a simplified version of adhesion, and for instructions to download and run a Java jarfile of the simulation.
in the meantime, check out some of the simulation movies here to see some of the things that Morphogenie can do.
