Membrane localization accelerates association under conditions relevant to cellular signaling

Proc Natl Acad Sci U S A. 2024 Mar 5;121(10):e2319491121. doi: 10.1073/pnas.2319491121. Epub 2024 Mar 1.

Abstract

Translocation of cytoplasmic molecules to the plasma membrane is commonplace in cell signaling. Membrane localization has been hypothesized to increase intermolecular association rates; however, it has also been argued that association should be faster in the cytosol because membrane diffusion is slow. Here, we directly compare an identical association reaction, the binding of complementary DNA strands, in solution and on supported membranes. The measured rate constants show that for a 10-µm-radius spherical cell, association is 22- to 33-fold faster at the membrane than in the cytoplasm. The kinetic advantage depends on cell size and is essentially negligible for typical ~1 µm prokaryotic cells. The rate enhancement is attributable to a combination of higher encounter rates in two dimensions and a higher reaction probability per encounter.

Keywords: Ras activation; bimolecular reaction; membrane-associated proteins; receptor signaling; reduction of dimensionality.

MeSH terms

  • Cell Membrane / metabolism
  • Cytoplasm / metabolism
  • Cytosol / metabolism
  • Kinetics
  • Membranes
  • Signal Transduction*