A milling crowd model for local and long-range obstructed lateral diffusion. Mobility of excimeric probes in the membrane of intact erythrocytes

Abstract

A new model for lateral diffusion, the milling crowd model (MC), is proposed and is used to derive the dependence of the monomeric and excimeric fluorescence yields of excimeric membrane probes on their concentration. According to the MC model, probes migrate by performing spatial exchanges with a randomly chosen nearest neighbor (lipid or probe). Only nearest neighbor probes, one of which is in the excited state, may form an excimer. The exchange frequency, and hence the local lateral diffusion coefficient, may then be determined from experiment with the aid of computer simulation of the excimer formation kinetics. The same model is also used to study the long-range lateral diffusion coefficient of probes in the presence of obstacles (e.g., membrane proteins). The dependence of the monomeric and excimeric fluorescence yields of 1-pyrene-dodecanoic acid probes on their concentration in the membranes of intact erythrocytes was measured and compared with the prediction of the MC model. The analysis yields an excimer formation rate for nearest neighbor molecules of approximately 1 X 10(7) s-1 and an exchange frequency of approximately greater than 2 X 10(7) s-1, corresponding to a local diffusion coefficient of greater than 3 X 10(-8) cm2 s-1. This value is several times larger than the long-range diffusion coefficient for a similar system measured in fluorescence photobleaching recovery experiments. The difference is explained by the fact that long-range diffusion is obstructed by dispersed membrane proteins and is therefore greatly reduced when compared to free diffusion. The dependence of the diffusion coefficient on the fractional area covered by obstacles and on their size is derived from MC simulations and is compared to those of other theories lateral diffusibility.

Consequences of ω-6-Oleate Desaturase Deficiency on Lipid Dynamics and Functional Properties of Mitochondrial Membranes ofArabidopsis thaliana

“…By contrast, lipid lateral diffusion measured in liposomes made from the mitochondrial lipids showed that (i) the difference between the two membranes was much smaller (50% only); (ii) there was no difference between liposomes and mitochondrial membranes in fad2 system, indicating that the high lipid mobility found in mutant mitochondrial membranes was mainly due to its low protein density. This hypothesis is in good agreement with reports showing that lateral diffusion of lipids in complex membranes is significantly reduced when proteins are incorporated in the bilayer (31,32). On the other hand, it is interesting to note that the activation energy of lipid lateral diffusion was lower in wild type mitochondrial membranes than in fad2 membranes or in liposomes.…”

Cholesteryl ester diffusion, location and self-association constraints determine CETP activity with discoidal HDL: Excimer probe study

“…6) may indicate the temperature-induced dissociation of ground-state complex, the common event in static quenching [22,25] or in a more subtle way, the decrease of viscosity-mediated diffusional constraints. Additionally, the obstacled diffusion per se [34] due to protein circumference in small rHDL may appreciably contribute into lower D L values obtained for CPD diffusion in the present study in comparison to other studies of lateral diffusion in larger membrane structures [20,23,34].…”

“…The coefficients of lateral diffusion calculated with Eqs. (1) and (2) for diffusion of the whole probe population (Table 1) varied as 2 10 À8 cm 2 s À1 for rHDL with POPC to 0.3 10 À8 cm 2 s À1 for rHDL with DPPC, being lower D L values (10 À8 -10 À7 cm 2 s À1 ) obtained for lateral diffusion in large membrane structures with pyrene excimerization and other approaches [20,23,34]. However, the difference markedly diminished after adjustment of D L values for probe fraction capable to fast exchange in CETP reaction (Table 1).…”

Lateral diffusion of lipids in complex biological membranes.

“…Eisinger et al (24) recently published a model for lipid diffusion in complex membranes. In this model, impermeable domains such as proteins are spatially fixed, unlike the model developed in this paper.…”