Role of Molecular Flexibility and Colloidal Descriptions of Proteins in Crowded Environments from Small-Angle Scattering.

Small-angle scattering is a powerful technique to study molecular conformation and interactions of proteins in solution and in amorphous solids. We have investigated the role of multiple protein configurations in the interaction parameters derived from small-angle scattering for proteins in concentrated solutions. In order to account for the wide configurational space sampled by proteins, we generate ensembles of atomistic structures for lysozyme and monoclonal antibodies, representing globular and flexible proteins, respectively.

Determination of biomembrane bending moduli in fully atomistic simulations.

The bilayer bending modulus (Kc) is one of the most important physical constants characterizing lipid membranes, but precisely measuring it is a challenge, both experimentally and computationally. Experimental measurements on chemically identical bilayers often differ depending upon the techniques employed, and robust simulation results have previously been limited to coarse-grained models (at varying levels of resolution). This Communication demonstrates the extraction of Kc from fully atomistic molecular dynamics simulations for three different single-component lipid bilayers (DPPC, DOPC, and DOPE).

Probing the average local structure of biomolecules using small-angle scattering and scaling laws.

Small-angle neutron and x-ray scattering have become invaluable tools for probing the nanostructure of molecules in solution. It was recently shown that the definite integral of the scattering profile exhibits a scaling (power-law) behavior with respect to molecular mass. We derive the origin of this relationship, and discuss how the integrated scattering profile can be used to identify differing levels of disorder over local ≲30 Å length scales.

Thermal fluctuations in shape, thickness, and molecular orientation in lipid bilayers. II. Finite surface tensions.

We investigate the role of lipid chemical potential on the shape, thickness, and molecular orientation (lipid tilting relative to the monolayer surface normal) of lipid bilayers via a continuum-level model. We predict that decreasing the chemical potential at constant temperature, which is associated with an increase in surface tension via the Gibbs-Duhem relation, leads both to the well known reduction in thermal membrane undulations and also to increasing fluctuation amplitudes for bilayer thickness and molecular orientation. These trends are shown to be in good agreement with molecular simulations, however it is impossible to achieve full quantitative agreement between theory and simulation within the confines of the present model.

Determining biomembrane bending rigidities from simulations of modest size.

Thermal fluctuations of lipid orientation are analyzed to infer the bending rigidity of lipid bilayers directly from molecular simulations. Compared to the traditional analysis of thermal membrane undulations, the proposed method is reliable down to shorter wavelengths and allows for determination of the bending rigidity using smaller simulation boxes. The requisite theoretical arguments behind this analysis are presented and verified by simulations spanning a diverse range of lipid models from the literature.

Thermal fluctuations in shape, thickness, and molecular orientation in lipid bilayers.

We present a unified continuum-level model for bilayer energetics that includes the effects of bending, compression, lipid orientation (tilting relative to the monolayer surface normal), and microscopic noise (protrusions). Expressions for thermal fluctuation amplitudes of several physical quantities are derived. These predictions are shown to be in good agreement with molecular simulations.

The intermediate scattering function for lipid bilayer membranes: from nanometers to microns.

A numerical scheme based upon established hydrodynamic and elastic considerations is introduced and used to predict the intermediate scattering function for lipid bilayer membranes. The predictions span multiple wavelength regimes, including those studied by dynamic light scattering (DLS; microns) and neutron spin-echo (NSE) spectroscopy (10-100 nm). The results validate a recent theory specific to the NSE regime and expose slight inaccuracies associated with the theoretical results available in the DLS regime.

Interpreting membrane scattering experiments at the mesoscale: the contribution of dissipation within the bilayer.

Neutron spin-echo spectroscopy provides a means to study membrane undulation dynamics over length scales roughly spanning 10-100 nanometers. Modern interpretation of these measurements relies on the theoretical predictions of Zilman and Granek; however, it is necessary to introduce an anomalously large solvent viscosity within this theory to obtain quantitative agreement with experiment. An extended theoretical treatment is presented that includes the effects of internal dissipation within the bilayer.