Cholesterol is often found
distributed nonrandomly in domains in biological
and model membranes and has been reported to be distributed
heterogeneously among various intracellular
membranes. While a large body of literature exists on
the organization of cholesterol in plasma
membranes or membranes  with high cholesterol content,
very little is known about organization of cholesterol
in membranes containing low amounts
of cholesterol. We
have previously shown using a fluorescent
cholesterol analogue (25-NBD-cholesterol)
that cholesterol may exhibit
local organization even at very low
concentrations in membranes as evidenced by
the presence of transbilay er tail- to -tail
dimers (Mukherjee and Chattopadhyay (1996) Biochemistry).
We have further investigated the
role of membrane curvature and thickness
on transbilayer dimer arrangement of cholesterol
using NBD-cholesterol. We find that dimerization
is not favored in membranes with high curvature. However,
cholesterol dimers are observed again if
the curvature stress is relieved. In
addition, we have monitored the effect
of membrane thickness on the dimerization
process. Our results show that
the dimerization process is
stringently controlled by a narrow window
of membrane thickness (Rukmini
et al. (2001) Biophys. J.). We
also monitored the microenvironmental
features of cholesterol monomers
and dimers using wavelength-selective
fluorescence. The environment around
the dimers appears to be more rigid
(Mukherjee and Chattopadhyay (2005) Chem.
Phys. Lipids). We have recently
explored the lateral diffusion of the
monomer and dimer populations using a novel
wavelength-selective FRAP approach (Pucadyil
et al. (2007) J. Phys. Chem. B). These results
could be relevant in membranes that have very low cholesterol content
such as the endoplasmic reticulum and the
inner mitochondrial membrane, and in trafficking and sorting
of cellular cholesterol.
Novel Organization of Cholesterol in Membranes at Low Concentrations: Effects of Curvature Stress and Membrane Thickness