A theoretical study of the contact region between lipid vesicles. Are the rate of fusion and the lateral phase separation of the membrane's lipid components related phenomena?

Abstract

A dynamic model of the contact region between two lipid vesicles has been developed. This region has been depicted as two superimposed vibrating plates bearing on their surfaces freely moving charges which are electrically balanced by their counter-ion distribution in the surrounding aqueous phase. The charges mimic the ionic head groups of the charged lipid molecules. Starting from an initial random distribution, the charges, rearrange themselves under the time-varying electric field originating from the mechanical oscillations of the two interacting lipid bilayers. This problem leads to coupled integro-differential equations describing the vibrational motions of the two membrances and the diffusion motion of the charged lipid molecules within the bilayers. These equation have been solved by a perturbation technique and the tow main results are as follows. First, in the zeroth-order approximation, a lowering of the vibrational frequencies with respect to those calculated, assuming a random distribution of charged and neutral lipids, is observed. This effect is accompanied by time-dependent fluctuation of the charted lipid concentration within the bilayer. Secondly, in the first-order approximation a new phenomenon takes place. A permanent (time-independent) lateral phase separation, forming domains richer in one lipid component, is predicted. This is not a thermodynamic phase separation, but a dynamic effect which is sustained by the mechanical fluctuations of the two interaction membrances. In the limit of very small amplitudes of vibration, as well as for very high friction coefficients for the lipids motion within the membrane, this effects tends to zero. The lowering of the vibrational frequencies in the zeroth-order approximation implies the increasing of thickness fluctuations in the contact region. Since the fusion process between lipid the vesicles takes place when the thickness fluctuations reach some critical values, the factors raising the amplitudes of vibration favour both faster kinetics of fusion and, according to the first-order calculation, wider lateral phase separations.

Preliminary numerical calculations show no appreciable lateral phase separation for weak interactions between the lipid bilayers. However, when very strong interactions leading to a destabilization of the lipid matrix are present, the formation of micro-domains is likely. Since in the early stages of the fusion processes the destabilization of the bilayer structure is an essential requisite, it follows that the lateral phase separation of the lipid components in the contact region is a consequence of rather than precedent to the fusion process.