Biomedical subjects

Laura J Douglas Frink

Publications and source records attributed to Laura J Douglas Frink.

4 recordsLinked to original sources

PubMed2006

Computational investigations of pore forming peptide assemblies in lipid bilayers.

This Letter presents the first application of a three-dimensional numerical molecular theory based modeling approach to study the structure and energetics of assemblies of peptides embedded in lipid bilayers. Coarse-grained models were used for both the peptides and lipids. Both barrel-stave and toroidal pore morphologies for the lipids near the peptide assemblies are found, but at different assembly sizes. The free energy of the assembly is found to have a global free energy minimum for a solution with a membrane-spanning toroidal pore. A pairwise approximation to this free energy is found to underpredict the free energy minimum associated with the membrane-spanning pores.

Algorithms↗

PubMed2006

Alcohols reduce lateral membrane pressures: predictions from molecular theory.

We explore the effects of alcohols on fluid lipid bilayers using a molecular theory with a coarse-grained model. We show that the trends predicted from the theory in the changes in area per lipid, alcohol concentration in the bilayer, and area compressibility modulus, as a function of alcohol chain length and of the alcohol concentration in the solvent far from the bilayer, follow those found experimentally. We then use the theory to study the effect of added alcohol on the lateral pressure profile across the membrane, and find that added alcohol reduces the surface tensions at both the headgroup/solvent and headgroup/tailgroup interfaces, as well as the lateral pressures in the headgroup and tailgroup regions. These changes in lateral pressures could affect the conformations of membrane proteins, providing a nonspecific mechanism for the biological effects of alcohols on cells.

Alcohols↗

PubMed2005

Density functional theory approach for coarse-grained lipid bilayers.

Lipid bilayers are important inhomogeneous fluid systems that mediate the environment of cells and the interaction of cells with their environment. A variety of approaches have been taken to model the lipid molecules in bilayers, from all atom molecular dynamics to rigid body liquid crystals. In this paper we discuss the application of a density functional theory approach that treats the lipid molecules at the coarse-grained level of a freely jointed chain. This approach allows for compressibility effects, and can therefore be used to study not only the long range structure in lipid bilayers, but also the nanoscale structure induced in the bilayer when the lipids crystallize or when an inclusion (e.g., an embedded protein) is present. This paper presents a detailed analysis of fluid bilayers and lamellae predicted by the theory. In particular we locate solutions with zero surface tension. We calculate the phase diagram for all possible phases with planar symmetry, including uniform macrophases. Surprisingly, we find a first-order phase transition from the lamellar phase to an isolated bilayer phase on lowering the temperature. This transition appears to be driven by solvent packing effects. A further lowering of the temperature leads to a set of highly ordered bilayers.

Computer Simulation↗

PubMed2005

Comparison of density functional theory and simulation of fluid bilayers.

We compare results of classical density functional theory (DFT) to molecular dynamics (MD) simulations of coarse-grained models of lipids in solvent. We find that the DFT captures the liquid structure of coarse-grained lipids both near surfaces and in bilayers adequately. In contrast we find that the MD simulations do not predict ordering in bilayers as is observed in low temperature DFT calculations. The mechanical properties of the fluid DFT bilayers are qualitatively similar to those of the MD bilayers; in particular the shapes of the lateral stress profiles are similar. Values of the area compressibility modulus are in reasonable agreement with previous work on coarse-grained lipids.

Computer Simulation↗