Tuning Protein Diffusivity with Membrane Tethers

Biochemistry. 2019 Jan 22;58(3):177-181. doi: 10.1021/acs.biochem.8b01150. Epub 2018 Dec 24.


Diffusion is essential for biochemical processes because it dominates molecular movement on small scales. Enzymatic reactions, for example, require fast exchange of substrate and product molecules in the local environment of the enzyme to ensure efficient turnover. On larger spatial scales, diffusion of secreted signaling proteins is thought to limit the spatial extent of tissue differentiation during embryonic development. While it is possible to measure diffusion in vivo, specifically interfering with diffusion processes and testing diffusion models directly remains challenging. The development of genetically encoded nanobodies that bind specific proteins has provided the opportunity to alter protein localization and reduce protein mobility. Here, we extend the nanobody toolbox with a membrane-tethered low-affinity diffusion regulator that can be used to tune the effective diffusivity of extracellular molecules over an order of magnitude in living embryos. This opens new avenues for future applications to functionally interfere with diffusion-dependent processes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Biochemistry / methods*
  • Cell Membrane / chemistry
  • Diffusion
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism
  • Embryo, Nonmammalian
  • Green Fluorescent Proteins / chemistry
  • Green Fluorescent Proteins / genetics
  • Immobilized Proteins / chemistry
  • Luminescent Proteins / genetics
  • Proteins / chemistry*
  • Proteins / genetics
  • Proteins / metabolism
  • Red Fluorescent Protein
  • Signal Transduction
  • Single-Domain Antibodies / chemistry
  • Single-Domain Antibodies / metabolism*
  • Zebrafish / embryology


  • Drosophila Proteins
  • Immobilized Proteins
  • Luminescent Proteins
  • Proteins
  • Single-Domain Antibodies
  • dpp protein, Drosophila
  • Green Fluorescent Proteins