A Monte Carlo simulation study of protein-induced heat capacity changes and lipid-induced protein clustering.

Monte Carlo simulations were used to describe the interaction of peripheral and integral proteins with lipids in terms of heat capacity profiles and protein distribution. The simulations were based on a two-state model for the lipid, representing the lipid state as being either gel or fluid. The interaction between neighboring lipids has been taken into account through an unlike nearest neighbor free energy term delta omega, which is a measure of the cooperativity of the lipid transition. Lipid/protein interaction was considered using the experimental observation that the transition midpoints of lipid membranes are shifted upon protein binding, a thermodynamic consequence of different binding constants of protein with fluid or gel lipids. The difference of the binding free energies was used as an additional parameter to describe lipid-protein interaction. The heat capacity profiles of lipid/protein complexes could be well described for both peripheral and integral proteins. Binding of proteins results in a shift and an asymmetric broadening of the melting profile. The model results in a coexistence of gel and fluid lipid domains in the proximity of the thermotropic transition. As a consequence, bound peripheral proteins aggregate in the temperature range of the lipid transition. Integral proteins induce calorimetric melting curves that are qualitatively different from that of peripheral proteins and aggregate in either gel or liquid crystalline lipid phase. The results presented here are in good agreement with calorimetric experiments on lipid-protein complexes and have implementations for the functional control of proteins

Simulation of the gel-fluid transition in a membrane composed of lipids with two connected acyl chains: application of a dimer-move step.

Phospholipids have been treated as dimers on a hexagonal lattice, and a move has been introduced that allows the dimers to move and change their orientation on the lattice. Simulations have been performed in which phospholipid chains have been treated as being either independent or infinitely coupled thermodynamically with regard to their conformational state. Both types of simulation have reproduced well experimental heat-capacity curves of dipalmitoyl phosphatidylcholine small unilamellar vesicles. Apart from a different gel-fluid interaction parameter and a different number of unlike nearest-neighbor contacts, most of the averages and thermodynamic quantities were essentially the same in the two types of simulation. These results indicate that the transition is not first order and validate those of previous Monte Carlo simulations that have neglected the dimeric nature of phospholipids in the sense that they show that for the thermotropic transition the approximation of phospholipids as monomers is valid

A macroscopic description of lipid bilayer phase transitions of mixed-chain phosphatidylcholines: chain-length and chain-asymmetry dependence.

A macroscopic model is presented to quantitatively describe lipid bilayer gel to fluid phase transitions. In this model, the Gibbs potential of the lipid bilayer is expressed in terms of a single order parameter q, the average chain orientational order parameter. The Gibbs potential is based on molecular mean-field and statistical mechanical calculations of inter and intrachain interactions. Chain-length and chain-asymmetry are incorporated into the Gibbs potential so that one equation provides an accurate description of mixed-chain phosphatidylcholines of a single class. Two general classes of lipids are studied in this work: lipid bilayers of partially or noninterdigitated gel phases, and bilayers of mixed interdigitated gel phases. The model parameters are obtained by fitting the transition temperature and enthalpy data of phosphatidylcholines to the model. The proposed model provides estimates for the transition temperature and enthalpy, van der Waals energy, number of gauche bonds, chain orientational order parameter, and bond rotational and excluded volume entropies, achieving excellent agreement with existing data obtained with various techniques