Biomedical subjects

Grace Brannigan

Publications and source records attributed to Grace Brannigan.

7 recordsLinked to original sources

PubMed2006

Contributions of Gaussian curvature and nonconstant lipid volume to protein deformation of lipid bilayers.

An elastic model for membrane deformations induced by integral membrane proteins is presented. An earlier theory is extended to account for nonvanishing saddle splay modulus within lipid monolayers and perturbations to lipid volume proximal to the protein. Analytical results are derived for the deformation profile surrounding a single cylindrical protein inclusion, which compare favorably to coarse-grained simulations over a range of protein sizes. Numerical results for multi-protein systems indicate that membrane-mediated interactions between inclusions are strongly affected by Gaussian curvature and display nonpairwise additivity. Implications for the aggregation of proteins are discussed.

Cell Membrane↗

PubMed2005

A consistent model for thermal fluctuations and protein-induced deformations in lipid bilayers.

We present an elastic Hamiltonian for membrane energetics that captures bilayer undulation and peristaltic deformations over all wavelengths, including the short wavelength protrusion regime. The model implies continuous functional forms for thermal undulation and peristaltic amplitudes as a function of wavelength and predicts previously overlooked relationships between these curves. Undulation and peristaltic spectra display excellent agreement with data from both atomistic and coarse-grained models over all simulated length scales. Additionally, the model accurately predicts the bilayer's response to a cylindrical protein inclusion as observed in coarse-grained simulation. This elastic response provides an explanation for gramicidin ion channel lifetime versus membrane thickness data that requires no fit constants. The physical parameters inherent to this picture may be expressed in terms of familiar material properties associated with lipid monolayers. Inclusion of a finite monolayer spontaneous curvature is essential to obtain fully consistent agreement between theory and the full range of available simulation/experimental data.

Computer Simulation↗

PubMed2005

Implicit solvent simulation models for biomembranes.

Fully atomic simulation strategies are infeasible for the study of many processes of interest to membrane biology, biophysics and biochemistry. We review various coarse-grained simulation methodologies with special emphasis on methods and models that do not require the explicit simulation of water. Examples from our own research demonstrate that such models have potential for simulating a variety of biologically relevant phenomena at the membrane surface.

Biophysical Phenomena↗

PubMed2005

Flexible lipid bilayers in implicit solvent.

A minimalist simulation model for lipid bilayers is presented. Each lipid is represented by a flexible chain of beads in implicit solvent. The hydrophobic effect is mimicked through an intermolecular pair potential localized at the "water"/hydrocarbon tail interface. This potential guarantees realistic interfacial tensions for lipids in a bilayer geometry. Lipids self-assemble into bilayer structures that display fluidity and elastic properties consistent with experimental model membrane systems. Varying molecular flexibility allows for tuning of elastic moduli and area per molecule over a range of values seen in experimental systems.

Biophysics↗

PubMed2005

Composition dependence of bilayer elasticity.

A previously developed molecular level model for homogeneous lipid bilayers [Brannigan and Brown, J. Chem. Phys 120, 1059 (2004)] is extended to allow for multiple lipid species. Monte Carlo simulations (including species exchange moves for efficient sampling) reveal a variety of mixing behaviors in binary systems. Two species are identified that maintain stable, randomly mixed fluid membranes at vanishing tension over all possible binary compositions. The thermal and elastic properties of membranes formed by these lipids are characterized over the full composition range. Equilibrium area at constant tension is nonmonotonic with respect to composition, but consistent with that of a quadratic mixture. In the constant tension ensemble, the bending rigidity of the bilayer is minimized at an intermediate composition. The observed functional form of bending rigidity vs composition is fit to a simple expression motivated by linear elasticity theory; this expression accounts for membrane heterogeneity through a single parameter.

Journal Article↗

PubMed2004

The role of molecular shape in bilayer elasticity and phase behavior.

A previously developed molecular level model for lipid bilayers [G. Brannigan and F. L. H. Brown, J. Chem. Phys. 120, 1059 (2004)] is extended to allow for variations in lipid length and simulations under constant surface tension conditions. The dependence of membrane elasticity on bilayer thickness is obtained by adjusting lipid length at constant temperature and surface tension. Additionally, bilayer fluidity at various lipid lengths is quantified by analysis of a length versus temperature phase diagram at vanishing tension. Regions of solid, gel-like (hexatic) and fluid bilayer behavior are established by identification of phase boundaries. The main melting transition is found to be density driven; the melting temperature scales inversely with lipid length since thermal expansion increases with lipid aspect ratio.

Journal Article↗

PubMed2004

Solvent-free simulations of fluid membrane bilayers.

A molecular level model for lipid bilayers is presented. Lipids are represented by rigid, asymmetric, soft spherocylinders in implicit solvent. A simple three parameter potential between pairs of lipids gives rise to a rich assortment of phases including (but not limited to) micelles, fluid bilayers, and gel-like bilayers. Monte Carlo simulations have been carried out to verify self-assembly, characterize the phases corresponding to different potential parametrizations, and to quantify the physical properties associated with those parameter sets corresponding to fluid bilayer behavior. The studied fluid bilayers have compressibility moduli in agreement with experimental systems, but display bending moduli at least three times larger than typical biological membranes without cholesterol.

Computer Simulation↗