Flagellar control of molecular motors

: Biophysical Modelling and Experimental Validation

Abstract

Flagella and cilia are versatile cellular appendages that play critical biological roles, from enabling spermatozoa motility to driving the clearance of mucus in the lungs. Within a flagellum, dynein molecular motors are anchored along a cylindrical arrangement of microtubules. The mechanism by which travelling waves of curvature emerge at the microscale from the collective activity of the motors at the nanoscale is an open question. An understanding of the origin of these waves is crucial for designing effective medical interventions when the intended function of either motility or fluid pumping breaks down. Although much work has been done in the modelling of candidate mechanisms, comparatively few attempts to fit experimental data have been made. In this thesis we model the flagellar beat of bull spermatozoa and C. Reinhardtii using a minimal reaction-diffusion system. This model successfully captures spatio-temporal patterns analogous to chemical reactions, suggesting a unified mechanism for molecular motor dynamics in flagella. We present an asymptotic analysis of the reaction-diffusion model, allowing us to predict key microscale beat pattern observables from nanoscale chemomechanical parameters. The decoupling of our model into a shaping problem and a swimming problem is emphasised, which may be a key tool for the study of flagellar control mechanisms going forward. Overall, this thesis underscores the importance of nonlinear dynamical models in the study of flagellar dynamics and demonstrates how analytical, computational and inferential techniques can yield insights into the underlying biophysical processes.

Date of Award	17 Jun 2025
Original language	English
Awarding Institution	University of Bristol
Supervisor	Hermes Gadelha (Supervisor) & Alan R Champneys (Supervisor)