Most biological molecules contain acido-basic groups that modulate their structure and interactions. A consequence is that pH gradients, local heterogeneities and dynamic variations are used by cells and organisms to drive or regulate specific biological functions including energetic metabolism, vesicular traffic, migration and spatial patterning of tissues in development. While the direct or regulatory role of pH in protein function is well documented, the role of hydrogen and hydroxyl ions in modulating the properties of lipid assemblies such as bilayer membranes is only beginning to be understood. Here, we review approaches using artificial lipid vesicles that have been instrumental in providing an understanding of the influence of pH gradients and local variations on membrane vectorial motional processes: migration, membrane curvature effects promoting global or local deformations, crowding generation by segregative polarization processes. In the case of pH induced local deformations, an extensive theoretical framework is given and an application to a specific biological issue, namely the structure and stability of mitochondrial cristae, is described. This article is part of a Special Issue entitled: Emergence of Complex Behavior in Biomembranes edited by Marjorie Longo.

We demonstrate migration of phospholipid vesicles in response to a pH gradient. Upon simple micro-injection of a NaOH solution, the vesicles linearly moved to the tip of the micro-pipette and the migration velocity was proportional to the gradient of OH(-) concentration. Vesicle migration was characteristic of OH(-) ions and no migration was observed for monovalent salts or nonionic sucrose solutions. The migration of vesicles is quantitatively described by the surface tension gradient model where the hydrolysis of the phospholipids by NaOH solution decreases the surface tension of the vesicle. The vesicles move toward a direction where the surface energy decreases. Thus the chemical modification of lipids produces a mechanical force to drive vesicles.

We have investigated the migrations of phospholipid vesicles under the concentration gradients of metal ions. We microinjected metal chloride solutions, monovalent (NaCl and KCl), divalent (CaCl and MgCl), and trivalent (LaCl) salts, toward phospholipid giant vesicles (GVs) composed of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC). For NaCl, CaCl, and MgCl solutions, the GVs migrated straight toward the tip of the micropipette in response to the concentration gradients, whereas for KCl and LaCl, GVs moved to the opposite direction. Our motion tracking of lipid domains in a vesicle membrane showed no unidirectional flow in the membrane during the vesicle migration, indicating that the Marangoni mechanism is not responsible for the observed vesicle migration. We calculated the diffusiophoretic velocities for symmetric and asymmetrical electrolytes by solving the Stokes' equation numerically. The theoretical diffusiophoretic velocities described the observed migration velocities well. Thus, we can control the migration of vesicle in response to the concentration gradient by adapting the electrolytes and the lipids.

We investigate the dynamics of decanoic acid/decanoate (DA) vesicles in response to pH stimuli. Two types of dynamic processes induced by the micro-injection of NaOH solutions are sequentially observed: deformations and topological transitions. In the deformation stage, DA vesicles show a series of shape deformations, i.e., prolate-oblate-stomatocyte-sphere. In the topological transition stage, spherical DA vesicles follow either of the two pathways, pore formation and vesicle fusion. The pH stimuli modify a critical aggregation concentration of DA molecules, which causes the solubilization of DA molecules in the outer leaflet of the vesicle bilayers. This solubilization decreases the outer surface area of the vesicle, thereby increasing surface tension. A kinetic model based on area difference elasticity theory can accurately describe the dynamics of DA vesicles triggered by pH stimuli.