A framework for an organelle-based mathematical modeling of hyphae

Rudibert King

Although highly desirable, a mechanistic explanation for the outstanding protein secretion capabilities of fungi such as Aspergilli is missing. As a result, a rational and predictive design of strains as cell factories for protein production is still out of reach. The analysis of the secretion apparatus is not only hampered by open issues concerning molecular cell biological processes, but as well by their spatial fragmentation and highly dynamic features. Whereas the former issues are addressed by many groups, an account of the space- and time-dependent processes, which is best done by means of mathematical models, is lacking. Up to now, mathematical models for hyphal organisms mainly focus on one of two extremes. Either macroscopic morphology, such as pellet or mycelium growth, is addressed, or a microscopic picture is drawn predicting, for instance, the form of a hyphal tip. How intra-hyphal transport and organelle distribution works, however, has not been tackled so far mathematically. The main result of this contribution is a generic modeling framework to describe the space- and time-dependent evolution of intracellular substances and organelles. It takes intrahyphal, passive and active transport of substances into account and explains exponential and then linear length growth by tugor-driven uptake of water. Experimentally observed increasing concentration levels of organelles towards the tip can be well explained within the framework without resorting to complex biological regulations. It is shown that the accumulation can be partly explained by geometrical constraints, besides a necessary deceleration of the active transport velocity. The model is formulated such that more intricate intracellular processes can be included. Results from steady-state experiments are easy to be interpreted. In a hyphal network, however, new branches are produced at an exponential rate. Moreover, passive and active transport processes give rise to a spatial distribution of organelles and other cytoplasmatic constituents inside hyphae. As a result, most of the data obtained in experiments will be from a non-steady and space dependent state. A quantitative and mechanistic explanation of the processes occurring will only be possible if these dependencies are taking into account while evaluating experimental findings.