April 18, Mon 2011
2:00 pm, MRB 200 Conference Room
Dr. Jian Dai
Department of Physics, Texas Tech University
A Comprehensive Study of Multi-Component Biomembranes Containing Cholesterol
In this work, various effects of cholesterol on cell membranes were investigated, including the umbrella model, the condensing effect, the phase boundary of lipid mixture containing cholesterol and cholesterolâ€™s resistance against the lytic antimicrobial peptide melittin.
The instability of cholesterol clusters and the umbrella effect of cholesterol in DPPC and DOPC lipid bilayers were investigated via atomistic molecular dynamics (MD) simulations. Cholesterol clusters in the phospholipid (PC) bilayers are found to be very unstable and to readily disperse into cholesterol monomers. Analysis also reveals that the PC headgroups surrounding cholesterol have a clear tendency to reorient and extend toward cholesterol. This study demonstrates that the umbrella hypothesis is valid in both saturated and unsaturated lipid bilayers. Monte-Carlo simulations were conducted to match a recently-constructed ternary phase diagram of lipid mixture. The liquid-ordered and liquid-disordered (lo-ld) phase boundary of DSPC/DOPC/Cholesterol mixtures is simulated in a lattice model using pairwise interactions. A â€œbest-fitâ€ﾝ phase boundary was obtained that has a top boundary closely resembling the experimental boundary. However, the results show that pairwise interactions alone are not sufficient to describe molecular interaction in the ternary lipid mixtures; multi-body interaction must be included in the simulation. The antimicrobial peptide melittin, is shown to cause membrane lyses, however, its lytic activity depends on the lipid composition of the membrane. MD simulations were used to study the modulation of melittin activity by cholesterol and negatively-charged phospholipid. A pure DPPC bilayer was used as a control. Bilayers with cholesterol and negatively-charged phospholipids showed strong resistance to melittin; at the mean time, the pure DPPC bilayer was deformed significantly with the introduction of melittin. These observations are consistent with experimental results.