Building Cellular Complexity: from Molecular Motors to Synthetic Cilia

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Molecular motors are nanoscale machines that convert chemical energy from ATP hydrolysis into mechanical movement along a filamentous track. Over the past two decades experimental advances have yielded remarkable images of single molecular motors taking nanometer-sized steps. Furthermore, state-of-the-art technology also makes it possible to pull on such nanomachines with optical traps thus determining the maximal force they can exert. Taken together these efforts have provided essential insight into biochemical mechanisms driving the motility of isolated molecular motors. However in many instances, ranging from contraction of a skeletal muscle to spontaneous beating of a biological cilium, motors do not act in isolation. Instead, thousands of motors coordinate their activity to produce large scale molecular motion. Despite its importance, little is known about the emergent collective properties of molecular motor ensembles. The first goal of this project is to develop an experimental assay that will quantify contractile sliding forces between a pair of aligned microtubules, exerted by molecular motor clusters that simultaneously bind and move along both filaments. Such structural motifs drive numerous complex processes in a biological cell. Using this information, the project will build microtubule bundles that are clamped at their base and driven by molecular motors. Theoretical models predict that such structures will spontaneous beat, thus mimicking the dynamical behavior of biological cilia. Experimental efforts will directly verify this prediction and provide insight into the mechanisms that control beating patterns of biological cilia. In parallel with experimental efforts, this project will also pursue development of computer simulation models for collective behavior of molecular motors; these will bridge the gap between existing theoretical models and experimental data. Broader Impacts: The research and outreach efforts will be seamlessly integrated through a mutual emphasis on visualization and microscopy. Movies of dynamical biological structures obtained via microscopy capture the imagination and interest of scientists and non-scientists alike. The PIs will organize outreach activities at The Discovery Museum in Acton, MA, in which optical microscopes and specimens will be available at the museum, allowing visitors to peer into the microscopic world and directly visualize biological motion. The PIs will also disseminate practical knowledge of optical microscopy by teaching an intensive hands-on one-week summer course. Investigator involvement with the highly successful science Posse program will further enhance undergraduate and graduate student involvement from historically underrepresented groups.