Membrane properties that vary as a result of isotropic and transmembra
ne osmolality variations (osmotic stress) are of considerable relevanc
e to mechanisms such as osmoregulation, in which a biological system '
'senses'' and responds to changes in the osmotic environment. In this
paper the light-scattering behavior of a model system consisting of la
rge unilamellar vesicles of dioleoyl phosphatidyl glycerol (DOPG) is e
xamined as a function of their osmotic environment. Osmotic downshifts
lead to marked reductions in the scattered intensity, whereas osmotic
upshifts lead to strong intensity increases. It is shown that these c
hanges in the scattering intensity involve changes in the refractive i
ndex of the membrane bilayer that result from an alteration in the ext
ent of hydration and/or the phospholipid packing density, By consideri
ng the energetics of osmotically stressed vesicles, and from explicit
analysis of the Rayleigh-Gans-Debye scattering factors for spherical a
nd ellipsoidal shells, we quantitatively demonstrate that although cha
nges in vesicle volume and shape can arise in response to the impositi
on of osmotic stress, these factors alone cannot account for the obser
ved changes in scattered intensity.