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Jun 27, 2014

Particles Rely on “Dirty Velcro” in Model of Cross-Membrane Transport

Particles Rely on “Dirty Velcro” in Model of Cross-Membrane Transport

“Dirtied” molecular Velcro is sticky enough to bind selected objects but weak enough to permit their two-dimensional diffusion. [Biozentrum, University of Basel]

  • The nuclear membrane is porous, but the pores are lined with proteins that may facilitate or retard the passage of different particles. Some particles, it seems, have the right kind of surface. These particles stick to the inner surface of a nuclear pore—but not too tightly. It is as if they are able to use a molecular-scale version of Velcro.

    Once stuck, the particles are constrained. That is, their diffusional wanderings are limited to the pore’s surface. Non-sticking particles keep floating in three dimensions, and so they are less likely to travel through the pore.

    Granted, in our macroscale world, an object fixed by means of Velcro cannot slide to and fro. But at the nanoscale, things work a little differently.

    To make sense of nanoscale Velcro, researchers at the University of Basel, the University of Cambridge, and the École Polytechnique Fédérale de Lausanne created an artificial model of the nuclear pore complex. This model, which appeared June 15 in Nature Nanotechnology, reconstituted the “two-dimensional diffusion of colloidal particles on a molecular brush surface.”

    In the artificial system, nuclear pores were lined with Velcro-like proteins—phenylalanine-glycine nucleoporins (FG nups), which are known to facilitate selective transport through nuclear pore complexes in eukaryotic cells. Further, binding to FG nups was possible only for particles specially marked with import proteins. Such binding, however, could be too strong.

    Particles to be transported need to bind; however, they should not bind so tightly that even two-dimensional diffusion (diffusion along the pore’s inner surface) is restrained.

    The researchers found that particles could be made to stick more or less tightly depending on whether the Velcro-like surface was filled or “dirtied” with import proteins. The details were spelled out in the Nature Nanotechnology article, which was entitled “Selective transport control on molecular Velcro made from intrinsically disordered proteins”.

    “Local and ensemble-level experiments involving optical trapping using a photonic force microscope and particle tracking by video microscopy, respectively, reveal that 1 µm-sized colloidal particles bearing nuclear transport receptors called karyopherins can exhibit behavior that varies from highly localized to unhindered two-dimensional diffusion,” wrote the authors. “Particle diffusivity is controlled by varying the amount of free karyopherins in solution, which modulates the multivalency of Kap-binding sites within the molecular brush.”

    The authors concluded that FG Nups resemble stimuli-responsive molecular Velcro that can impart a “reduction of dimensionality” as a means of biomimetic transport control in artificial environments.
    “Understanding how the transport process functions in the nuclear pore complex was decisive for our discovery,” explained Roderick Lim, Ph.D., a professor at the University of Basel. “With the nanoscale ‘Velcro’ we should be able to define the path to be taken as well as speed up the transport of selected particles without requiring external energy.”

    Practical applications, added Dr. Lim, might include nanoscale conveyor belts, escalators, or tracks. In addition, the “dirty Velcro” effect could be applied to further miniaturize lab-on-chip technology, tiny labs on chips, where this newly discovered method of transportation could make today’s complex pump and valve systems obsolete.


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