Thermal fluctuations and osmotic stability of lipid vesicles

Biological membranes constantly change their shape in response to external stimuli, and understanding the remodeling and stability of vesicles in heterogeneous environments is therefore of fundamental importance for a range of cellular processes. One crucial question is how vesicles respond to external osmotic stresses, imposed by differences in solute concentrations between the vesicle interior and exterior. Previous analyses of the membrane bending energy have predicted that micron-sized giant unilamellar vesicles (GUVs) should become globally deformed already for nanomolar concentration differences, in contrast to experimental findings that find deformations at much higher osmotic stresses. In this article, we analyze the mechanical stability of a spherical vesicle exposed to an external osmotic pressure in a statistical-mechanical model, including the effect of thermally excited membrane bending modes. We find that the inclusion of thermal fluctuations of the vesicle shape changes renders the vesicle deformation continuous, in contrast to the abrupt transition in the athermal picture. Crucially, however, the predicted critical pressure associated with global vesicle deformation remains the same as when thermal fluctuations are neglected, approximately six orders of magnitude smaller than the typical collapse pressure recently observed experimentally for GUVs. We conclude by discussing possible sources of this persisting dissonance between theory and experiments.