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Selective transport control on molecular velcro made from intrinsically disordered proteins

Nature Nanotechnology volume 9, pages 525–530 (2014)Cite this article

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Abstract

The selectivity and speed of many biological transport processes1 transpire from a ‘reduction of dimensionality’2 that confines diffusion to one or two dimensions instead of three3. This behaviour remains highly sought after on polymeric surfaces4 as a means to expedite diffusional search processes in molecular engineered systems. Here, we have reconstituted the two-dimensional diffusion of colloidal particles on a molecular brush surface. The surface is composed of phenylalanine-glycine nucleoporins (FG Nups)5—intrinsically disordered proteins that facilitate selective transport through nuclear pore complexes in eukaryotic cells6. Local and ensemble-level experiments involving optical trapping using a photonic force microscope7 and particle tracking by video microscopy8, respectively, reveal that 1-µm-sized colloidal particles bearing nuclear transport receptors9 called karyopherins can exhibit behaviour that varies from highly localized to unhindered two-dimensional diffusion. Particle diffusivity is controlled by varying the amount of free karyopherins in solution, which modulates the multivalency of Kap-binding sites within the molecular brush10. We conclude that the FG Nups resemble stimuli-responsive11 molecular ‘velcro’, which can impart ‘reduction of dimensionality’ as a means of biomimetic transport control in artificial environments.

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Figure 1: Influence of Kapβ1 concentration on Kap-probe binding and mobility.
Figure 2: Changes to local Kap-probe diffusivity with increasing Kapβ1 concentration.
Figure 3: Effect of Kapβ1 concentration on ensemble Kap-probe probability distribution and lateral diffusivity.
Figure 4: Reduction of dimensionality by the ‘dirty velcro effect’.

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Acknowledgements

The authors thank R.L. Schoch, M. Grimm and F.M. Mor for assistance and discussions. R.Y.H.L., K.D.S. and L.E.K. acknowledge support from the National Centre of Competence in Research ‘Molecular Systems Engineering’, the Swiss National Science Foundation, the Biozentrum and the Swiss Nanoscience Institute. S.J. acknowledges support from the Swiss National Science Foundation (SNF grant nos R'Equip 206021_121396 and 200021_143703). S.L.D. acknowledges the German Academic Exchange Service and the German National Academic Foundation. S.P. and U.F.K. acknowledge support from an ERC starting grant. S.P. also acknowledges support from the Leverhulme and Newton Trust through an Early Career Fellowship.

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Authors and Affiliations

  1. Biozentrum and the Swiss Nanoscience Institute, University of Basel, Klingelbergstrasse 50/70 CH – 4056, Basel, Switzerland

    Kai D. Schleicher, Larisa E. Kapinos & Roderick Y. H. Lim

  2. Cavendish Laboratory, University of Cambridge, Cambridge, CB3 0HE, UK

    Simon L. Dettmer, Stefano Pagliara & Ulrich F. Keyser

  3. Biozentrum, University of Basel and the Laboratory of Physics of Complex Matter, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland

    Sylvia Jeney

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Contributions

K.D.S. conceived and carried out the experiments, wrote the manuscript, and analysed and interpreted the data. S.L.D. developed the tracking software and analysed the data. S.P. developed the tracking software and analysed the data. L.E.K. contributed proteins and interpreted data. U.F.K. analysed and interpreted data. S.J. designed and built the experimental set-up, conceived the experiment and the PFM data analysis protocol. R.Y.H.L. conceived the experiment, interpreted data and wrote the manuscript. All authors contributed to, discussed and commented on the manuscript.

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Correspondence to Roderick Y. H. Lim.

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Schleicher, K., Dettmer, S., Kapinos, L. et al. Selective transport control on molecular velcro made from intrinsically disordered proteins. Nature Nanotech 9, 525–530 (2014). https://doi.org/10.1038/nnano.2014.103

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