A5025990340- Lipid Membrane Structure and Behavior
- Nanopore and Nanochannel Transport Studies
- RNA Interference and Gene Delivery
- Spectroscopy and Quantum Chemical Studies
- Protein Structure and Dynamics
- Force Microscopy Techniques and Applications
- Photoreceptor and optogenetics research
- RNA and protein synthesis mechanisms
- Sphingolipid Metabolism and Signaling
- ATP Synthase and ATPases Research
- Antimicrobial Peptides and Activities
- Supramolecular Self-Assembly in Materials
- Electrostatics and Colloid Interactions
- Advanced Electron Microscopy Techniques and Applications
- Electrochemical Analysis and Applications
- Neuroscience and Neural Engineering
- Viral gastroenteritis research and epidemiology
- Surfactants and Colloidal Systems
- Advanced NMR Techniques and Applications
- Erythrocyte Function and Pathophysiology
- Enzyme Structure and Function
- Bacterial Genetics and Biotechnology
- Escherichia coli research studies
- Fatty Acid Research and Health
- Nuclear Physics and Applications
Oak Ridge National Laboratory
2019-2025
University of Tennessee at Knoxville
2015-2024
Significance Cholesterol regulates critical cell functions, including lysis, viral budding, and antibiotic resistance, by modifying the bending rigidity of membranes; i.e., ability membranes to bend or withstand mechanical stresses. A molecular-level understanding these functions requires knowledge how cholesterol modifies membrane mechanics over relevant length time scales. Currently, it is widely accepted that has no effect on properties unsaturated lipid membranes, implying viruses, for...
Significance We have used cryogenic electron microscopy (cryo-EM) to achieve direct, probe-free imaging of lateral domains in biomimetic lipid membranes under native conditions and characterize differences their structures. First, measurements membrane thickness laterally uniform single-component show that cryo-EM is capable subangstrom resolution interleaflet thickness. All-atom simulations are predict the appearance submicron vesicles with coexisting liquid these quantitatively validated...
Biological supramolecular assemblies, such as phospholipid bilayer membranes, have been used to demonstrate signal processing via short-term synaptic plasticity (STP) in the form of paired pulse facilitation and depression, emulating brain's efficiency flexible cognitive capabilities. However, STP memory lipid bilayers is volatile cannot be stored or accessed over relevant periods time, a key requirement for learning. Using droplet interface (DIBs) composed lipids, water hexadecane, an...
Several diseases, such as cancer, are characterized by acidification of the extracellular environment. Acidosis can be employed a target to specifically direct therapies diseased tissue. We have used first principles design an acidity-triggered rational membrane (ATRAM) peptide with high solubility in solution that is able interact lipid membranes pH-dependent fashion. Biophysical studies show ATRAM binds surface at pH 8.0. However, leads inserting into bilayer transmembrane α-helix. The...
Despite the prevalence of lipid transbilayer asymmetry in natural plasma membranes, most biomimetic model membranes studied are symmetric. Recent advances have helped to overcome difficulties preparing asymmetric liposomes vitro, allowing for examination a larger set relevant biophysical questions. Here, we investigate stability bilayers by measuring flip-flop with time-resolved small-angle neutron scattering (SANS). Asymmetric large unilamellar vesicles inner bilayer leaflets containing...
Solvent toxicity limits n-butanol fermentation titer, increasing the cost and energy consumption for subsequent separation processes making biobased production more expensive energy-intensive than petrochemical approaches. Amphiphilic solvents such as partition into cell membrane of fermenting microorganisms, thinning transverse structure, eventually causing a loss potential death. In this work, we demonstrate deleterious effects partitioning upon lateral dimension called domains or lipid...
We have determined the fluid bilayer structure of palmitoyl sphingomyelin (PSM) and stearoyl (SSM) by simultaneously analyzing small-angle neutron X-ray scattering data. Using a newly developed density profile (SDP) model for lipids, we report structural parameters including area per lipid, total thickness, hydrocarbon in addition to lipid volumes densitometry. Unconstrained all-atom simulations PSM bilayers at 55 °C using C36 CHARMM force field produced 56 Å2, value that is 10% lower than...
It is well known that the lipid distribution in bilayer leaflets of mammalian plasma membranes (PMs) not symmetric. Despite this, model membrane studies have largely relied on chemically symmetric for study lipid–lipid and lipid–protein interactions. This primarily due to difficulty preparing stable, asymmetric are amenable biophysical studies. However, last 20 years, efforts been made producing more biologically faithful membranes. Here, we review several recently developed experimental...
The pH-low insertion peptide (pHLIP) targets acidic diseases such as cancer. acidity of the environment causes key aspartic acids in pHLIP to become protonated, causing insert into membranes. Here we investigate how negative charge membrane influences enters and exits lipid bilayer. We found that electrostatic repulsion affected differently entry exit for negatively charged As a consequence, large hysteresis was observed. propose this is not consequence structural changes but results from...
Abstract We studied the transleaflet coupling of compositionally asymmetric liposomes in fluid phase. The vesicles were produced by cyclodextrin-mediated lipid exchange and contained dipalmitoyl phosphatidylcholine (DPPC) inner leaflet different mixed-chain phosphatidylcholines (PCs) as well milk sphingomyelin (MSM) outer leaflet. In order to jointly analyze obtained small-angle neutron X-ray scattering data, we adapted existing models trans-bilayer structures measure overlap hydrocarbon...
Phospholipid bilayers can be described as capacitors whose capacitance per unit area (specific capacitance, Cm) is determined by their thickness and dielectric constant─independent of applied voltage. It also widely assumed that the Cm membranes treated a "biological constant". Recently, using droplet interface (DIBs), it was shown zwitterionic phosphatidylcholine (PC) lipid act voltage-dependent, nonlinear memory capacitors, or memcapacitors. When exposed to an electrical "training"...
We report the real-time response of
Based on neutron spin-echo (NSE), solid-state NMR, and molecular dynamics (MD) simulations, we report clear evidence that cholesterol stiffens 1,2-dioleoyl- sn -glycero-3-phosphocholine (DOPC) membranes (1). Contrary to statements by Nagle et al. (2), the relaxations measured NSE NMR directly relate elastic membrane constants (3, 4). While both spectroscopy measure time-averaged 𝜏 -decay, 〈 A ( t ) + τ 〉 , data analysis methods separate mean-square amplitude (MSA) from dynamics, providing...
Abstract The underlying principles for generating intelligent behavior in living organisms are fundamentally different from those traditional solid‐state circuits. Biomimetic neuromorphic equivalents based on biological membranes offer novel implementation of tunable plasticity and diverse mechanisms to control functionality. Here, dynamic electrochemical impedance spectroscopy (dEIS) probe diphytanoylphosphatidylcholine (DPhPC) droplet interface bilayers (DIBs) better understand the...
Cryogenic electron microscopy (cryo-EM) is among the most powerful tools available for interrogating nanoscale structure of biological materials. We recently showed that cryo-EM can be used to measure bilayer thickness lipid vesicles and membranes with subangstrom precision, resulting in direct visualization nanoscopic domains different multicomponent mixtures giant plasma membrane vesicles. Despite great potential revealing lateral organization biomembranes, a large parameter space...
We addressed the frequent occurrence of mixed-chain lipids in biological membranes and their impact on membrane structure by studying several chain-asymmetric phosphatidylcholines highly asymmetric milk sphingomyelin. Specifically, we report trans-membrane structures corresponding fluid lamellar phases using small-angle X-ray neutron scattering, which were jointly analyzed terms a composition-specific model, including headgroup hydration shell. Focusing terminal methyl groups at bilayer...
In biology, heterosynaptic plasticity maintains homeostasis in synaptic inputs during associative learning and memory, initiates long-term changes strengths that nonspecifically modulate different synapse types. bioinspired neuromorphic circuits, may be used to extend the functionality of two-terminal, biomimetic memristors. this article, we explore how pH droplet interface bilayer aqueous solutions memristive responses a lipid membrane range 4.97-7.40. Surprisingly, did not find conclusive...
A previously reported multi-scale model for (ultra-)small-angle X-ray (USAXS/SAXS) and (very) small-angle neutron scattering (VSANS/SANS) of live Escherichia coli was revised on the basis compositional/metabolomic ultrastructural constraints. The cellular body is modeled, as described, by an ellipsoid with multiple shells. However, originating from flagella replaced a term accounting oligosaccharide cores lipopolysaccharide leaflet outer membrane including its cross-term body. This mainly...
Differential scanning calorimetry (DSC) of dipalmitoyl phosphatidylcholine (DPPC), dihexanoyl phosphatidylcholine, and phosphatidylglycerol bicelles reveals two endothermic peaks. Based on analysis small angle neutron scattering X-ray data, the DSC peaks are associated with melting DPPC a change in bicellar morphology─namely, either bicelle-to-spherical vesicle or oblate-to-spherical vesicle. The reversibility structural transformations was examined by found to be consistent corresponding...