Mechanisms of selective transport through nuclear pore complex mimics

ORAL

Abstract

Few cellular processes require such intricate active control as transport through the nuclear envelope. The nuclear pore complex (NPC) facilitates all transport, preventing most macromolecules from crossing the envelope while allowing the passage of transport factors (TFs) and their cargo. While the basic biochemical interactions of transport are well-understood, the detailed mechanism remains a topic of significant debate. We create tunable mimics of the NPC using PEG hydrogels filled with FG nucleoporins (FG nups), the intrinsically disordered proteins that line the NPC channel in vivo. We also model transport using reaction-diffusion equations. The results suggest that (1) the flexible nature of the disordered FG nups and (2) the transient, multivalent nature of FG nup -- TF interactions are together sufficient for selectivity. Our model makes selectivity predictions that will be directly testable in our experimental setup. We aim to use the model to tune the mimic's parameters to maximize selectivity.

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Authors

  • Laura Maguire

    University of Colorado Boulder

  • Colin Roberts

    High Precision Devices, Boulder, CO, Raytheon, Tucson, AZ, Seagate Technology, Minneapolis, MN, Ball Aerospace (retired), Bloomfield, CO, New Mexico State University, Brigham Young University, Colorado State University, Heinrich-Heine-Universitat Dusseldorf, National Security Technologies, Universidad de Buenos Aires, Colorado State Univ, Colorado College, Utah State University, Advisor, Material Physics Group, Utah State University, Box Elder Innovations, LLC, JILA and Department of Physics, CU Boulder, JILA and Department of Mathematics, CU Boulder, Colorado State University, Fort Collins, Colorado 80523, USA, JILA, NIST and the University of Colorado, Boulder, NIST, University of Colorado / NIST, University of Colorado/JILA, Colorado Sch of Mines, Colorado School of Mines, Southwestern Indian Polytechnic Institute, UC-Berkeley, Colorado State University, Fort Collins, CO, Wroclaw University of Science and Technology, Wroclaw, Poland, JILA, University of Colorado and NIST, Harvard University and Harvard-MIT Center for Ultracold Atoms, Univ of Colorado - Boulder, USAFA, Univ of Denver, Boyce Research Initiatives and Educational Foundation, Brilliant Sky Observatory, San Diego Mesa College, Utah Valley University, University of Colorado Boulder, Brigham Young Univ - Provo, Oak Ridge National Laboratory, University of Sherbrooke, NIST Boulder, Universidad Complutense de Madrid, Electrical and Computer Engineering Department, Colorado State University, Fort Collins, Co 80525, Lawrence Livermore National Lab. (United States), Physics Department, Colorado State University, Fort Collins, Co 80525, JILA, Department of Physics, University of Colorado Boulder, Los Alamos National Laboratory, University of Alabama, University of Wyoming, University of Guelph, University of Guelph, Canadian Light source

  • Colin Roberts

    High Precision Devices, Boulder, CO, Raytheon, Tucson, AZ, Seagate Technology, Minneapolis, MN, Ball Aerospace (retired), Bloomfield, CO, New Mexico State University, Brigham Young University, Colorado State University, Heinrich-Heine-Universitat Dusseldorf, National Security Technologies, Universidad de Buenos Aires, Colorado State Univ, Colorado College, Utah State University, Advisor, Material Physics Group, Utah State University, Box Elder Innovations, LLC, JILA and Department of Physics, CU Boulder, JILA and Department of Mathematics, CU Boulder, Colorado State University, Fort Collins, Colorado 80523, USA, JILA, NIST and the University of Colorado, Boulder, NIST, University of Colorado / NIST, University of Colorado/JILA, Colorado Sch of Mines, Colorado School of Mines, Southwestern Indian Polytechnic Institute, UC-Berkeley, Colorado State University, Fort Collins, CO, Wroclaw University of Science and Technology, Wroclaw, Poland, JILA, University of Colorado and NIST, Harvard University and Harvard-MIT Center for Ultracold Atoms, Univ of Colorado - Boulder, USAFA, Univ of Denver, Boyce Research Initiatives and Educational Foundation, Brilliant Sky Observatory, San Diego Mesa College, Utah Valley University, University of Colorado Boulder, Brigham Young Univ - Provo, Oak Ridge National Laboratory, University of Sherbrooke, NIST Boulder, Universidad Complutense de Madrid, Electrical and Computer Engineering Department, Colorado State University, Fort Collins, Co 80525, Lawrence Livermore National Lab. (United States), Physics Department, Colorado State University, Fort Collins, Co 80525, JILA, Department of Physics, University of Colorado Boulder, Los Alamos National Laboratory, University of Alabama, University of Wyoming, University of Guelph, University of Guelph, Canadian Light source

  • Colin Roberts

    High Precision Devices, Boulder, CO, Raytheon, Tucson, AZ, Seagate Technology, Minneapolis, MN, Ball Aerospace (retired), Bloomfield, CO, New Mexico State University, Brigham Young University, Colorado State University, Heinrich-Heine-Universitat Dusseldorf, National Security Technologies, Universidad de Buenos Aires, Colorado State Univ, Colorado College, Utah State University, Advisor, Material Physics Group, Utah State University, Box Elder Innovations, LLC, JILA and Department of Physics, CU Boulder, JILA and Department of Mathematics, CU Boulder, Colorado State University, Fort Collins, Colorado 80523, USA, JILA, NIST and the University of Colorado, Boulder, NIST, University of Colorado / NIST, University of Colorado/JILA, Colorado Sch of Mines, Colorado School of Mines, Southwestern Indian Polytechnic Institute, UC-Berkeley, Colorado State University, Fort Collins, CO, Wroclaw University of Science and Technology, Wroclaw, Poland, JILA, University of Colorado and NIST, Harvard University and Harvard-MIT Center for Ultracold Atoms, Univ of Colorado - Boulder, USAFA, Univ of Denver, Boyce Research Initiatives and Educational Foundation, Brilliant Sky Observatory, San Diego Mesa College, Utah Valley University, University of Colorado Boulder, Brigham Young Univ - Provo, Oak Ridge National Laboratory, University of Sherbrooke, NIST Boulder, Universidad Complutense de Madrid, Electrical and Computer Engineering Department, Colorado State University, Fort Collins, Co 80525, Lawrence Livermore National Lab. (United States), Physics Department, Colorado State University, Fort Collins, Co 80525, JILA, Department of Physics, University of Colorado Boulder, Los Alamos National Laboratory, University of Alabama, University of Wyoming, University of Guelph, University of Guelph, Canadian Light source

  • Colin Roberts

    High Precision Devices, Boulder, CO, Raytheon, Tucson, AZ, Seagate Technology, Minneapolis, MN, Ball Aerospace (retired), Bloomfield, CO, New Mexico State University, Brigham Young University, Colorado State University, Heinrich-Heine-Universitat Dusseldorf, National Security Technologies, Universidad de Buenos Aires, Colorado State Univ, Colorado College, Utah State University, Advisor, Material Physics Group, Utah State University, Box Elder Innovations, LLC, JILA and Department of Physics, CU Boulder, JILA and Department of Mathematics, CU Boulder, Colorado State University, Fort Collins, Colorado 80523, USA, JILA, NIST and the University of Colorado, Boulder, NIST, University of Colorado / NIST, University of Colorado/JILA, Colorado Sch of Mines, Colorado School of Mines, Southwestern Indian Polytechnic Institute, UC-Berkeley, Colorado State University, Fort Collins, CO, Wroclaw University of Science and Technology, Wroclaw, Poland, JILA, University of Colorado and NIST, Harvard University and Harvard-MIT Center for Ultracold Atoms, Univ of Colorado - Boulder, USAFA, Univ of Denver, Boyce Research Initiatives and Educational Foundation, Brilliant Sky Observatory, San Diego Mesa College, Utah Valley University, University of Colorado Boulder, Brigham Young Univ - Provo, Oak Ridge National Laboratory, University of Sherbrooke, NIST Boulder, Universidad Complutense de Madrid, Electrical and Computer Engineering Department, Colorado State University, Fort Collins, Co 80525, Lawrence Livermore National Lab. (United States), Physics Department, Colorado State University, Fort Collins, Co 80525, JILA, Department of Physics, University of Colorado Boulder, Los Alamos National Laboratory, University of Alabama, University of Wyoming, University of Guelph, University of Guelph, Canadian Light source

  • Colin Roberts

    High Precision Devices, Boulder, CO, Raytheon, Tucson, AZ, Seagate Technology, Minneapolis, MN, Ball Aerospace (retired), Bloomfield, CO, New Mexico State University, Brigham Young University, Colorado State University, Heinrich-Heine-Universitat Dusseldorf, National Security Technologies, Universidad de Buenos Aires, Colorado State Univ, Colorado College, Utah State University, Advisor, Material Physics Group, Utah State University, Box Elder Innovations, LLC, JILA and Department of Physics, CU Boulder, JILA and Department of Mathematics, CU Boulder, Colorado State University, Fort Collins, Colorado 80523, USA, JILA, NIST and the University of Colorado, Boulder, NIST, University of Colorado / NIST, University of Colorado/JILA, Colorado Sch of Mines, Colorado School of Mines, Southwestern Indian Polytechnic Institute, UC-Berkeley, Colorado State University, Fort Collins, CO, Wroclaw University of Science and Technology, Wroclaw, Poland, JILA, University of Colorado and NIST, Harvard University and Harvard-MIT Center for Ultracold Atoms, Univ of Colorado - Boulder, USAFA, Univ of Denver, Boyce Research Initiatives and Educational Foundation, Brilliant Sky Observatory, San Diego Mesa College, Utah Valley University, University of Colorado Boulder, Brigham Young Univ - Provo, Oak Ridge National Laboratory, University of Sherbrooke, NIST Boulder, Universidad Complutense de Madrid, Electrical and Computer Engineering Department, Colorado State University, Fort Collins, Co 80525, Lawrence Livermore National Lab. (United States), Physics Department, Colorado State University, Fort Collins, Co 80525, JILA, Department of Physics, University of Colorado Boulder, Los Alamos National Laboratory, University of Alabama, University of Wyoming, University of Guelph, University of Guelph, Canadian Light source

  • Colin Roberts

    High Precision Devices, Boulder, CO, Raytheon, Tucson, AZ, Seagate Technology, Minneapolis, MN, Ball Aerospace (retired), Bloomfield, CO, New Mexico State University, Brigham Young University, Colorado State University, Heinrich-Heine-Universitat Dusseldorf, National Security Technologies, Universidad de Buenos Aires, Colorado State Univ, Colorado College, Utah State University, Advisor, Material Physics Group, Utah State University, Box Elder Innovations, LLC, JILA and Department of Physics, CU Boulder, JILA and Department of Mathematics, CU Boulder, Colorado State University, Fort Collins, Colorado 80523, USA, JILA, NIST and the University of Colorado, Boulder, NIST, University of Colorado / NIST, University of Colorado/JILA, Colorado Sch of Mines, Colorado School of Mines, Southwestern Indian Polytechnic Institute, UC-Berkeley, Colorado State University, Fort Collins, CO, Wroclaw University of Science and Technology, Wroclaw, Poland, JILA, University of Colorado and NIST, Harvard University and Harvard-MIT Center for Ultracold Atoms, Univ of Colorado - Boulder, USAFA, Univ of Denver, Boyce Research Initiatives and Educational Foundation, Brilliant Sky Observatory, San Diego Mesa College, Utah Valley University, University of Colorado Boulder, Brigham Young Univ - Provo, Oak Ridge National Laboratory, University of Sherbrooke, NIST Boulder, Universidad Complutense de Madrid, Electrical and Computer Engineering Department, Colorado State University, Fort Collins, Co 80525, Lawrence Livermore National Lab. (United States), Physics Department, Colorado State University, Fort Collins, Co 80525, JILA, Department of Physics, University of Colorado Boulder, Los Alamos National Laboratory, University of Alabama, University of Wyoming, University of Guelph, University of Guelph, Canadian Light source