Mesoscopic Monte Carlo simulations of stochastic encounters between photoactivated rhodopsin and transducin in disc membranes.
The issue of how the molecular organization of rod outer segments (ROS) discs affects the initial timing of the photoresponse in vertebrates has been recently raised by novel structural findings that raise doubts about the classical scenario of monomeric rhodopsin (R) and heterotrimeric transducin (G) freely diffusing in the membrane milieu. In this study, we investigate this issue by means of mesoscopic Monte Carlo (MMC) simulations of the stochastic encounters between one photoactivated R and one G, explicitly taking into account the molecular size and the diffusion coefficient of each species as well as crowding effects. Three different scenarios were compared with respect to their effects on timing, namely, (a) the classical framework, where both G and monomeric R are allowed to freely diffuse in the ROS disc membrane, (b) the ideal paracrystalline organization of R dimers considered as a structural unit, where ordered rows completely cover the disc membrane patch, and (c) the scenario suggested by recent AFM data, where R dimers organize in differently sized rafts with varying local concentrations. Our simulations suggest that a similar kinetic response could arise from very different microscopic scenarios, thus opening new interpretations to the controversial recent findings. Moreover, we show that if high-density R packing on ROS discs is characterized by a highly ordered structural organization rather than unspecific aggregation, an unexpected favorable effect on the temporal response of early phototransduction reactions can occur.
Dell'Orco
Daniele
D
Department of Chemistry, University of Modena and Reggio Emilia and Dulbecco Telethon Institute, via Campi 183 41100 Modena, Italy. daniele.dellorco@unimore.it
Schmidt
Henning
H
D000465:Algorithms; D000818:Animals; D004058:Diffusion; D008566:Membranes / Q000737:chemistry*; D008954:Models, Biological; D009010:Monte Carlo Method; D012243:Rhodopsin / Q000737:chemistry*; D012374:Rod Cell Outer Segment / Q000737:chemistry* / Q000648:ultrastructure; D013269:Stochastic Processes; D015293:Transducin / Q000737:chemistry*; D014785:Vision, Ocular
D012243:Rhodopsin; D015293:Transducin