Chalmers Conferences, 9th European Conference on Mathematical and Theoretical Biology

The effect of plasma membrane compartmentalization on receptor assembly dynamics
Andre Leier, Changjiang You, Tatiana T. Marquez-Lago, Jacob Piehler

Last modified: 2014-03-28

Abstract


Transport and communication across the plasma membrane frequently involves the association of transmembrane proteins into dimeric or oligomeric complexes. The interaction dynamics within these complexes is determined by two-dimensional association and dissociation rate constants. Nanoscale confinement of the interaction partners by the actin meshwork and microdomains in the plasma membrane has been speculated to play an important role for the dynamics of such protein complexes.

We combined experimental and computational methods to quantify the effects of plasma membrane compartmentalization on the assembly dynamics of type I interferon receptor complexes. A detailed computer model of the hierarchical membrane compartmentalization was developed. Simulation results of receptor dynamics were compared with those obtained from single molecule fluorescence microscopy experiments employing dual-colour quantum-dot (QD) labelling of receptor subunits.

High-resolution spatial stochastic simulations of receptor hop diffusion in our model membrane confirmed that confinement enables rapid re-association of dissociated signalling complexes in time frames similar to those of QD experiments. Control experiments were also reproduced with computer simulations.


Keywords


Receptor dynamics, membrane compartmentalization, spatial-stochastic simulations