A growth-fragmentation approach for modeling microtubule dynamic instability

Stephane Honore (1) , Florence Hubert (2) , Magali Tournus (2) , Diana White (2)

1 Service de Pharmacologie Clinique [Hôpital de la Timone - APHM]
2 I2M - Institut de Mathématiques de Marseille

Microtubules (MTs) are protein filaments found in all eukaryotic cells which are crucial for many cellular processes including cell movement, cell differentiation, and cell division. Due to their role in cell division, they are often used as targets for chemotherapy drugs used in cancer treatment. Experimental studies of MT dynamics have played an important role in the development and administration of many novel cancer drugs, however, a complete description of MT dynamics is lacking. Here, we propose a new mathematical model for MT dynamics, that can be used to study the effects of chemotherapy drugs on MT dynamics. Our model consists of a growth-fragmentation equation describing the dynamics of a density of MTs, coupled with two ODEs that describe the dynamics of free GTP-and GDP-tubulin concentrations (the individual dimers that comprise of MTs). We prove the well-posedness of our system and perform a numerical exploration of the influence of the parameters on the systems dynamics. This exploration helps provide insight into the action of MT-targeting chemotherapy drugs on MT dynamics.

Mots clés: Banach fixed point; Microtubules dynamics; Growth-fragmentation model

Domaines: Equations aux dérivées partielles [math.AP]; Sciences du Vivant [q-bio]

Stephane Honore, Florence Hubert, Magali Tournus, Diana White. A growth-fragmentation approach for modeling microtubule dynamic instability. Bulletin of Mathematical Biology, 2019, 81 (3), pp.722-758. ⟨10.1007/s11538-018-0531-2⟩. ⟨hal-01630658⟩