Effect of curvature and normal forces on motor regulation of cilia

TL;DR

This paper investigates how curvature and normal forces influence motor regulation in cilia, aiming to clarify feedback mechanisms that control their oscillatory beating patterns.

Contribution

It develops both linear and nonlinear models to analyze the role of forces and displacements in dynein regulation of cilia movement.

Findings

Identifies key forces regulating dynein activity

Compares predicted cilia shapes with experimental data

Provides insights into feedback mechanisms of cilia beating

Abstract

Cilia are ubiquitous organelles involves in eukaryotic motility. They are long, slender, and motile protrusions from the cell body. They undergo active regular oscillatory beating patterns that can propel cells, such as the algae Chlamydomonas, through fluids. When many cilia beat in synchrony they can also propel fluid along the surfaces of cells, as is the case of nodal cilia. The main structural elements inside the cilium are microtubules. There are also molecular motors of the dynein family that actively power the motion of the cilium. These motors transform chemical energy in the form of ATP into mechanical forces that produce sliding displacement between the microtubules. This sliding is converted to bending by constraints at the base and/or along the length of the cilium. Forces and displacements within the cilium can regulate dyneins and provide a feedback mechanism: the dyneins generate forces, deforming the cilium; the deformations, in turn, regulate the dyneins. This feedback is believed to be the origin of the coordination of dyneins in space and time which underlies the regularity of the beat pattern. Goals and approach. While the mechanism by which dyneins bend the cilium is understood, the feedback mechanism is much less clear. The two key questions are: which forces and displacements are the most relevant in regulating the beat? and how exactly does this regulation occur? In this thesis we develop a framework to describe the spatio-temporal patterns of a cilium with different mechanisms of motor regulation. Characterizing and comparing the predicted shapes and beat patterns of these different mechanisms to those observed in experiments provides us with further understanding on how dyneins are regulated. This comparison is done both, with a linear model that can be analytically solved, as with a non-linear model that we solve numerically.