A. Hinderliter et al., Domain formation in a fluid mixed lipid bilayer modulated through binding of the C2 protein motif, BIOCHEM, 40(13), 2001, pp. 4181-4191
The role and mechanism of formation of lipid domains in a functional membra
ne have generally received limited attention. Our approach, based on the hy
pothesis that thermodynamic coupling between lipid-lipid and protein-lipid
interactions can lead to domain formation, uses a combination of an experim
ental lipid bilayer model system and Monte Carlo computer simulations of a
simple model of that system. The experimental system is a fluid bilayer com
posed of a binary mixture of phosphatidylcholine (PC) and phosphatidylserin
e (PS), containing 4% of a pyrene-labeled anionic phospholipid. Addition of
the C2 protein motif (a structural domain found in proteins implicated in
eukaryotic signal transduction and cellular trafficking processes) to the b
ilayer first increases and then decreases the excimer/monomer ratio of the
pyrene fluorescence. We interpret this to mean that protein binding induces
anionic lipid domain formation until the anionic lipid becomes saturated w
ith protein. Monte Carlo simulations were performed on a lattice representi
ng the lipid bilayer to which proteins were added. The important parameters
are an unlike lipid-lipid interaction term and an experimentally derived p
referential protein-lipid interaction term. The simulations support the exp
erimental conclusion and indicate the existence of a maximum in PS domain s
ize as a function of protein concentration. Thus, lipid-protein coupling is
a possible mechanism for both lipid and protein clustering on a fluid bila
yer. Such domains could be precursors of larger lipid-protein clusters ('ra
fts'), which could be important in various biological processes such as sig
nal transduction at the level of the cell membrane.