Membrane localization accelerates association under conditions relevant to cellular signaling

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 in solution and on supported membranes. The measured rate constants show that for 10 m-radius spherical cell, association is 15-25-fold faster at the membrane than in the cytoplasm. The advantage is cell size-dependent, and for typical ~1 m prokaryotic cells it should be essentially negligible. Rate enhancement is attributable to a combination of closer proximity of the signaling molecule to its targets after translocation and the higher efficiency of a two-dimensional search.