title: A systematic comparison of mathematical models for inherent measurement of ciliary length: how a cell can measure length and volume.
abstract: Cells control organelle size with great precision and accuracy to maintain optimal physiology, but the mechanisms by which they do so are largely unknown. Cilia and flagella are simple organelles in which a single measurement, length, can represent size. Maintenance of flagellar length requires an active transport process known as intraflagellar transport, and previous measurements suggest that a length-dependent feedback regulates intraflagellar transport. But the question remains: how is a length-dependent signal produced to regulate intraflagellar transport appropriately? Several conceptual models have been suggested, but testing these models quantitatively requires that they be cast in mathematical form. Here, we derive a set of mathematical models that represent the main broad classes of hypothetical size-control mechanisms currently under consideration. We use these models to predict the relation between length and intraflagellar transport, and then compare the predicted relations for each model with experimental data. We find that three models-an initial bolus formation model, an ion current model, and a diffusion-based model-show particularly good agreement with available experimental data. The initial bolus and ion current models give mathematically equivalent predictions for length control, but fluorescence recovery after photobleaching experiments rule out the initial bolus model, suggesting that either the ion current model or a diffusion-based model is more likely correct. The general biophysical principles of the ion current and diffusion-based models presented here to measure cilia and flagellar length can be generalized to measure any membrane-bound organelle volume, such as the nucleus and endoplasmic reticulum.
authors: Department of Biophysics and Biochemistry, University of California, San Francisco, San Francisco, California.
authors: William B
authors: WB
authors: Ludington
authors: Department of Biophysics and Biochemistry, University of California, San Francisco, San Francisco, California.
authors: Hiroaki
authors: H
authors: Ishikawa
authors: Department of Biophysics and Biochemistry, University of California, San Francisco, San Francisco, California.
authors: Yevgeniy V
authors: YV
authors: Serebrenik
authors: Physiology Course, Marine Biological Laboratory, Woods Hole, Massachusetts.
authors: Alex
authors: A
authors: Ritter
authors: Physiology Course, Marine Biological Laboratory, Woods Hole, Massachusetts.
authors: Rogelio A
authors: RA
authors: Hernandez-Lopez
authors: Physiology Course, Marine Biological Laboratory, Woods Hole, Massachusetts.
authors: Julia
authors: J
authors: Gunzenhauser
authors: Department of Biophysics and Biochemistry, University of California, San Francisco, San Francisco, California.
authors: Elisa
authors: E
authors: Kannegaard
authors: Department of Biophysics and Biochemistry, University of California, San Francisco, San Francisco, California. Electronic address: wmarshall@biochem.ucsf.edu.
authors: Wallace F
authors: WF
authors: Marshall
mesh_terms: D002696:Chlamydomonas / Q000502:physiology*; D002923:Cilia / Q000502:physiology; D004058:Diffusion; D005407:Flagella / Q000502:physiology; D036681:Fluorescence Recovery After Photobleaching; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D007477:Ions / Q000378:metabolism; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D009068:Movement; D053141:Organelle Size; D013045:Species Specificity
chemical_list: D007477:Ions; D049452:Green Fluorescent Proteins