An Investigation of the Mechanism that Produces Rhythmic Beating in Cilia and Flagella

Oakland University, Rochester MI

Investigators

Abstract

Intellectual merit. Flagella and cilia are self-contained biological machines that convert chemical energy from ATP into useful mechanical work. They are basic organelles of living cells that are found in most animals and many plants. In mammals they play an important role in the development of an embryo, in respiration, and in reproduction. How these basic components of living cells work is still rather poorly understood and the goal of this project. The major approach is to gather vital physical information about the flagellum and to incorporate it into a detailed model of flagellar mechanics. To accomplish this goal, a unique set of tools has been developed. A technique that uses force-calibrated glass microprobes will be employed to measure the forces actively produced and the passive mechanical stiffness of flagella. Data will be analyzed using a unique and detailed computational model of the mechanics of the flagellum called the "Geometric Clutch model". To date, this model has successfully duplicated and even predicted much of the behavior of cilia and flagella. The model will be refined using the experimental data and will provide a framework to develop a complete picture of flagellar mechanics. The mechanical and physical information obtained from these studies will complement present understanding of the flagellum at a molecular level. Specifically, the Geometric Clutch model will allow mechanical properties of specific flagellar substructures to be correlated with defined molecular components. Both the algal model system, Chlamydomonas, with its extensive molecular biological database, and the mammalian sperm, with which the laboratory already has extensive experience, will be used for these studies. Broader impacts. This multidisciplinary project, which will apply physics and computational modeling to a biological investigation, will be of broad interest to the mathematics, physics, engineering, and cell biology communities. The flagellum is an example of an exquisite micro-machine of nature that will help us understand and harness the forces of molecular motors. The project has an extensive record of mentoring undergraduate students and introducing them to the principles and practice of laboratory research. It is expected that undergraduates involved in the project will be co-authors on scientific reports from these studies and will be motivated to pursue careers in science, teaching, and medicine.