Summary
Phosphatidyl ethanolamine (PE) is shown to be effective in producing membrane aggregation. The aggregation of PE and PE/PC (phosphatidyl choline) mixed vesicles was studied as a function of pH and cation composition of the medium. The kinetics and equilibria were studied in stopped-flow rapid mixing experiments, in which PE vesicles prepared at pH 9.2 were “jumped” to pH 7.
H+ ions protonate PE− and promote vesicle aggregation in a cooperative fashion. Vesicles containing PC have a decreased tendency to aggregate compared to pure PE vesicles. The apparent rate constant for aggregation was about two orders of magnitude below that for diffusion controlled aggregation and was virtually the same for PE and PE/PC mixed vesicles.
A theoretical description of equilibrium for vesicle aggregation is developed in terms of three parameters: the equilibrium constant for the protonation of PE (K A ), the equilibrium constant for aggregation (K eq) and the number of PE molecules in an effective area that the two vesicles must interact in order to aggregate (N eff). These parameters are compared with values and trends expected for electrostatic calculations based on dipolar repulsion and short-range binding, to which hydrogen bonding may contribute. The results are interpreted in a self-consistent fashion to indicate: (i) that PE and PC mix randomly, (ii) that head-to-tail binding occurs between PE(PC) molecules on apposing vesicles, (iii) that electrostatic screening accounts for the decrease inK A as a function of the molar fraction of PC per vesicle, (iv) that the PE must be 90% protonated before aggregation can occur, and (v) that for all the lipid systems we considered, the point at which the extent of dimerization is half maximal is close to the physiological pH, indicating that PE may have a regulatory effect in the aggregation of biological systems.
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Kolber, M.A., Haynes, D.H. Evidence for a role of phosphatidyl ethanolamine as a modulator of membrane-membrane contact. J. Membrain Biol. 48, 95–114 (1979). https://doi.org/10.1007/BF01869258
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DOI: https://doi.org/10.1007/BF01869258