Modeling of sensing potency of cytoskeletal systems decorated with metabolic enzymes

- The dynamic cytoskeleton interacts with proteins that are involved in metabolic or signaling pathways.
- Mathematical models for the interactions of metabolic pathways and microtubule assembly are evaluated.
- Functional consequences of these interactions are predicted in distinct situations.
- A kinetic model with relevant parameters reproduces altered tubulin assembly caused by a glycolytic enzyme.
- A mechanistic description allows the quantification of how cells sense the state of pathways.

The highly dynamic cytoskeleton interacts with enzymes and other proteins that are involved in metabolic or signaling pathways. These interactions can influence the structural and functional characteristics of the partners at the microscopic level of individual proteins and polymers. In this work the functional consequences of such interactions have been studied at the macroscopic level in order to evaluate the integrative and regulatory roles of the metabolic pathways associated with the microtubule cytoskeleton. Here we present mathematical models of the interactions between a hypothetical metabolic pathway and microtubule assembly, and explore for the first time the functional consequences of these interactions in distinct situations. The models include kinetic constants of the individual steps and testable, relevant parameters which allow the quantification of the coupled processes at the microscopic and macroscopic levels. For example our kinetic model for the self-assembly of microtubules reproduces the alteration of the time-dependent turbidity caused by pyruvate kinase binding. Our data reveal the power of a mechanistic description of a filamentous system to explain how cells sense the state of metabolic and other pathways.