Cytoskeleton and Cell Motility

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V. CYTOSKELETON AND CELL MOTILITY

V.1 COORDINATORS:

W. M. Saxton (Dept. of Biology, IUB). Associate Coordinators: S. Strome (Dept. of Biology, IUB), H. Goodson (Dept. of Chemistry and Biochemistry, ND). Theory Coordinator: G. Forgacs (Dept. of Physics, University of Missouri, Columbia)

V.2 PARTICIPANTS:

M. Alber (Dept. of Mathematics, ND), J. Glazier (Dept. of Physics, IUB), S. Gross (Dept. of Biomedical Physics and Dept. of Developmental and Cellular Biology, University of California, Irvine), J. Rubinstein (Dept. of Mathematics, IUB), J. Tang (Dept. of Physics, IUB), C. Walczak, (Dept. of Medical Sciences, IUB), J. White (Laboratory of Molecular Biology, University of Wisconsin).

V.3 INTRODUCTION:

Biological systems organize dynamically. A complex body plan relies on precise organization of tissues, each tissue relying on ordered associations of various types of cells, and those cells depending on internal ordering of subcellular components. The cytoskeleton, a system of dynamic filamentous polymers, crosslinkers, and force-producing "motor proteins," together with their spatial and temporal regulators, generates that internal order. Research on the dynamic behavior of the cytoskeleton and its role in different types of cells has provided the basic information needed to begin modeling cytoskeleton-associated mechanisms. We propose a set of collaborative projects to do so, focusing on the behavior of individual microtubules and microfilaments, the way that they organize to form networks, and how they are used for cytoplasmic movement. We aim to produce innovative approaches and substantial advances in our understanding of intracellular order.The microtubule cytoskeleton (microtubules, binding proteins, and motors) plays a fundamental role in the organization of almost all eukaryotic cell types; it assembles and positions the mitotic spindle, segregates the mitotic chromosomes to specific target areas, defines the plane of the cell division cleavage furrow, and constantly drives organelles into appropriate positions. We propose experiments that address how the microtubule cytoskeleton is assembled and how it functions, and propose the beginnings of modeling to establish a unifying theoretical framework.The dynamic and mechanical properties of the actin cytoskeleton endow the cell with the ability to change shape, to move, to resist stress, and respond to extracellular signals. These properties emerge from the complex interactions between actin filaments, free actin subunits, actin monomer/polymer binding proteins, and the signal transduction apparatus that regulates these proteins. To model the properties of the actin cytoskeleton in a quantitative and predictive way, we must identify the proteins that modulate actin polymerization and experimentally characterize their interactions with actin and their effects on actin polymerization. We also must define the mechanical properties of the actin network in connection with the dynamic assembly of the actin cytoskeleton.Mathematical models must integrate many experimental findings. We face the task of choosing the appropriate levels of detail to describe phenomena that span many orders of magnitude in size. Our initial modeling approaches will inevitably be flawed. As the experimental and theoretical projects proceed, we hope to develop more informed and consistent choices for the level of description and methodologies for describing molecular scale behavior and aggregating simulations into larger scale predictive models.