Biology subjects

Brown, M. F.

Publications and source records attributed to Brown, M. F..

4 recordsLinked to original sources

bioRxiv2026

Ultrafast X-Rays Capture Retinal Traversing Conical Intersection in Rhodopsin

G-protein-coupled receptors of the Rhodopsin family are crucial medicinal targets, transmitting signals across biomembranes. While light absorption by visual rhodopsin is well studied, its activation via retinal cofactor dynamics remains unclear. Here we use a free-electron laser to show that time-resolved X-ray solution scattering captures the retinal cis-trans isomerization as it passes the conical intersection of excited and ground-state photoproduct energy surfaces. Femtosecond-scale nuclear changes occur due to resonant photon absorption, with all-atom simulations revealing ultrafast amino acid movements that initiate transmembrane helix shifts. Ligand-free opsin measurements confirm that light activation is unaffected by non-resonant processes, showing the photonic energy is directly transmitted within the protein. Our method unveils how cofactor dynamics activate rhodopsin, free of constraints from crystal lattice packing or cryotrapping photointermediates.

biophysics↗

bioRxiv2023

Sampling Bottleneck in Validating Membrane Dynamics

Molecular dynamics simulations of lipid membranes have become increasingly impactful in biophysics because they offer atomistic resolution of structural fluctuations in relation to their functional outputs. Yet quantitative characterization of multiscale processes is a formidable challenge due to the distribution of motions that evade analysis of discrete simulation data. Here we investigate the efficient calculation of CH bond relaxation rates from membrane simulations. Widely used computational approaches offer numerical simplicity but fall short of capturing crucial aspects of the orientation dependence of the dynamics. To circumvent this problem, we introduced a robust framework based on liquid crystal theory which considers explicitly the CH bond motions with respect to the director axis (bilayer normal). Analysis of the orientation dependence of the dynamics shows excellent agreement with experiment, illustrating how the ordering potential affects the calculated relaxation rates. Furthermore, a fit-based resampling of the autocorrelation function of the bond fluctuations validates the new approach for low-temporal resolution data. The recovered relaxation rates indicate that at short timescales, both with and without cholesterol, the local motions of CH bonds describe the bilayer microviscosity and resemble liquid hydrocarbons. Our results establish the critical role of the orientational anisotropy in analysis of membrane simulations, explain fundamental aspects of lipid dynamics, and provide guidelines for extracting information that can be compared to experimental data. STATEMENT OF SIGNIFICANCENuclear magnetic resonance data have been historically used to validate membrane simulations through the average order parameters of the lipid chains. However, the bond dynamics that give rise to this equilibrium bilayer structure have rarely been compared between in vitro and in silico systems despite the availability of substantial experimental data. Here we investigate the logarithmic timescales sampled by the lipid chain motions and confirm a recently developed computational protocol that creates a dynamics-based bridge between simulations and NMR spectroscopy. Our results establish the foundations for validating a relatively unexplored dimension of bilayer behavior and thus have far-reaching applications in membrane biophysics.

biophysics↗

bioRxiv2022

Molecular Simulations and NMR Reveal How Lipid Fluctuations Affect Membrane Mechanics

Lipid bilayers form the main matrix of functional cell membranes, and their dynamics underlie a host of physical and biological processes. Here we show that elastic membrane properties and collective molecular dynamics are related by the mean-square amplitudes (order parameters) and relaxation rates (correlation times) of lipid acyl chain motions. We performed all-atom molecular dynamics simulations of liquid-crystalline bilayers to further interpret available NMR data. Our analysis entailed development of a theoretical framework that allows direct comparison of carbon-hydrogen (CH) bond relaxations as measured by simulations and NMR experiments. The new formalism enables validation of lipid force fields against NMR data by including a fixed bilayer normal (director axis) and restricted anisotropic motion of the CH bonds described by their segmental order parameters. The simulated spectral density of thermally excited CH bond fluctuations exhibited well-defined spin-lattice (Zeeman) relaxations analogous to those measured by solid-state NMR spectroscopy. Their frequency signature could be fit to a simple power-law function, indicative of collective dynamics of a nematic-like nature. The calculated spin-lattice relaxation rates scaled as the squared order parameters of the lipid acyl chains yielding an apparent bending modulus{kappa} C of the bilayer. Our results show a strong correlation with{kappa} C values obtained from solid-state NMR studies of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) bilayers with varying amounts of cholesterol as further validated by neutron spin-echo measurements of membrane elasticity. The simulations uncover a critical role of interleaflet coupling in membrane mechanics and thus provide insights into the molecular sites of emerging elastic properties within lipid bilayers. STATEMENT OF SIGNIFICANCEThe lipid make-up of a bilayer determines its measurable properties but how the motions of individual molecules combine to produce these properties remains unclear. By exploiting the synergy between NMR spectroscopy and molecular dynamics (MD) simulations, we show that the lipid dynamics in a bilayer are collective yet segmental in nature and contribute directly to bilayer elasticity. Comparison between MD simulations and NMR entails an improved theoretical framework that allows the two techniques to be directly related. This study thus provides novel insights into the inner workings of lipid membranes while delivering a new tool for validating computational approaches against experimental data.

biophysics↗

bioRxiv2020

No preference for prosocial 'helping' behavior in rats with concurrent social interaction opportunities

Helping behavior tasks are proposed to assess prosocial or empathic behavior in rodents. This paradigm characterizes the behavior of subject animals presented with the opportunity to release a conspecific from a distressing situation. Previous studies found a preference in rats for releasing restrained or distressed conspecifics over other controls (e.g., empty restrainers or inanimate objects). An empathy account was offered to explain the observed behaviors, claiming subjects were motivated to reduce the distress of others based on a rodent homologue of empathy. An opposing account attributes all previous results to subjects seeking social-contact. To dissociate these two accounts for helping behavior, we presented subject rats with three simultaneous choice alternatives: releasing a restrained conspecific, engaging a non-restrained conspecific, or not socializing. Subjects showed an initial preference for socializing with the non-restrained conspecific, and no preference for helping. This result contradicts the empathy account, but is consistent with the social-contact account of helping behavior.

animal behavior and cognition↗