Nucleation theory with delayed interactions: An application to the earlystages of the receptor-mediated adhesion/fusion kinetics of lipid vesicles

摘要

A semiquantitative theory aimed to describe the adhesion kinetics between soft objects, such asliving cells or vesicles, has been developed. When rigid bodies are considered, the adhesion kineticsis successfully described by the classical Derjaguin, Landau, Verwey, and Overbeek (DLVO)picture, where the energy profile of two approaching bodies is given by a two asymmetricalpotential wells separated by a barrier. The transition probability from the long-distance to theshort-distance minimum defines the adhesion rate. Conversely, soft bodies might follow a differentpathway to reach the short-distance minimum: thermally excited fluctuations give rise to localprotrusions connecting the approaching bodies. These transient adhesion sites are stabilized byshort-range adhesion forces (e.g., ligand-receptor interactions between membranes brought atcontact distance), while they are destabilized both by repulsive forces and by the elastic deformationenergy. Above a critical area of the contact site, the adhesion forces prevail: the contact site growsin size until the complete adhesion of the two bodies inside a short-distance minimum is attained.This nucleation mechanism has been developed in the framework of a nonequilibrium Fokker–Planck picture by considering both the adhesive patch growth and dissolution processes. In addition,we also investigated the effect of the ligand-receptor pairing kinetics at the adhesion site in the timecourse of the patch expansion. The ratio between the ligand-receptor pairing kinetics and theexpansion rate of the adhesion site is of paramount relevance in determining the overall nucleationrate. The theory enables one to self-consistently include both thermodynamics (energy barrierheight) and dynamic (viscosity) parameters, giving rise in some limiting cases to simple analyticalformulas. The model could be employed to rationalize fusion kinetics between vesicles, providedthe short-range adhesion transition is the rate-limiting step to the whole adhesion process.Approximate relationships between the experimental fusion rates reported in the literature andparameters such as membrane elastic bending modulus, repulsion strength, temperature, osmoticforces, ligand-receptor binding energy, solvent and membrane viscosities are satisfactory explainedby our model. The present results hint a possible role of the initial long-distance → short-distancetransition in determining the whole fusion kinetics.