RT Journal Article
SR Electronic
T1 The influence of molecular reach and diffusivity on the efficacy of membrane-confined reactions
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 439430
DO 10.1101/439430
A1 Ying Zhang
A1 Lara Clemens
A1 Jesse Goyette
A1 Jun Allard
A1 Omer Dushek
A1 Samuel. A. Isaacson
YR 2018
UL http://biorxiv.org/content/early/2018/10/10/439430.abstract
AB Signalling by surface receptors often relies on tethered reactions whereby an enzyme bound to the cytoplasmic tail f a receptor catalyses reactions on substrates within reach. The overall length and stiffness of the receptor tail, the enzyme, and the substrate determine a biophysical parameter termed the molecular reach of the reaction. This parameter determines the probability that the receptor-tethered-enzyme will contact the substrate, in the volume proximal to the membrane, when separated by different distances within the membrane plane. Here, we develop particle-based stochastic reaction-diffusion models to study the interplay between molecular reach and diffusion. We find that increasing the molecular reach can increase reaction efficacy when diffusion is slow, but when diffusion is fast, increasing molecular reach reduces reaction efficacy. This switching is lost if reactions are forced to take place within the 2D plasma membrane instead of the 3D volume proximal to it, or if molecules diffuse in 3D. We show results in the context of immune receptors (PD-1 dephosphorylating CD28), a standard opposing kinase-phosphatase reaction, and a minimal two-particle model. The work highlights the 3D nature of many 2D membrane-confined interactions, illustrating a role for molecular reach in controlling biochemical reactions.