Confinement in Nanodiscs Anisotropically Modifies Lipid Bilayer Elastic Properties

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11320%2F20%3A10423854" target="_blank" >RIV/00216208:11320/20:10423854 - isvavai.cz</a>

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=X_yKrQfOmk" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=X_yKrQfOmk</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/acs.jpcb.0c03374" target="_blank" >10.1021/acs.jpcb.0c03374</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Confinement in Nanodiscs Anisotropically Modifies Lipid Bilayer Elastic Properties

Popis výsledku v původním jazyce

Lipid nanodiscs are small synthetic lipid bilayer structures that are stabilized in solution by special circumscribing (or scaffolding) proteins or polymers. Because they create native-like environments for transmembrane proteins, lipid nanodiscs have become a powerful tool for structural determination of this class of systems when combined with cryo-electron microscopy or nuclear magnetic resonance. The elastic properties of lipid bilayers determine how the lipid environment responds to membrane protein perturbations, and how the lipid in turn modifies the conformational state of the embedded protein. However, despite the abundant use of nanodiscs in determining membrane protein structure, the elastic material properties of even pure lipid nanodiscs (i.e., without embedded proteins) have not yet been quantitatively investigated. A major hurdle is due to the inherently nonlocal treatment of the elastic properties of lipid systems implemented by most existing methods, both experimental and computational. In addition, these methods are best suited for very large &quot;infinite&quot; size lipidic assemblies, or ones that contain periodicity, in the case of simulations. We have previously described a computational analysis of molecular dynamics simulations designed to overcome these limitations, so it allows quantification of the bending rigidity (K-C) and tilt modulus (kappa(t)) on a local scale even for finite, nonperiodic systems, such as lipid nanodiscs. Here we use this computational approach to extract values of K-C and kappa(t) for a set of lipid nanodisc systems that vary in size and lipid composition. We find that the material properties of lipid nanodiscs are different from those of infinite bilayers of corresponding lipid composition, highlighting the effect of nanodisc confinement. Nanodiscs tend to show higher stiffness than their corresponding macroscopic bilayers, and moreover, their material properties vary spatially within them. For small-size MSP1 nanodiscs, the stiffness decreases radially, from a value that is larger in their center than the moduli of the corresponding bilayers by a factor of similar to 2-3. The larger nanodiscs (MSP1E3D1 and MSP2N2) show milder spatial changes of moduli that are composition dependent and can be maximal in the center or at some distance from it. These trends in moduli correlate with spatially varying structural properties, induding the area per lipid and the nanodisc thickness. Finally, as has previously been reported, nanodiscs tend to show deformations from perfectly flat circular geometries to varying degrees, depending on size and lipid composition. The modulations of lipid elastic properties that we find should be carefully considered when making structural and functional inferences concerning embedded proteins.

Název v anglickém jazyce

Confinement in Nanodiscs Anisotropically Modifies Lipid Bilayer Elastic Properties

Popis výsledku anglicky

Lipid nanodiscs are small synthetic lipid bilayer structures that are stabilized in solution by special circumscribing (or scaffolding) proteins or polymers. Because they create native-like environments for transmembrane proteins, lipid nanodiscs have become a powerful tool for structural determination of this class of systems when combined with cryo-electron microscopy or nuclear magnetic resonance. The elastic properties of lipid bilayers determine how the lipid environment responds to membrane protein perturbations, and how the lipid in turn modifies the conformational state of the embedded protein. However, despite the abundant use of nanodiscs in determining membrane protein structure, the elastic material properties of even pure lipid nanodiscs (i.e., without embedded proteins) have not yet been quantitatively investigated. A major hurdle is due to the inherently nonlocal treatment of the elastic properties of lipid systems implemented by most existing methods, both experimental and computational. In addition, these methods are best suited for very large &quot;infinite&quot; size lipidic assemblies, or ones that contain periodicity, in the case of simulations. We have previously described a computational analysis of molecular dynamics simulations designed to overcome these limitations, so it allows quantification of the bending rigidity (K-C) and tilt modulus (kappa(t)) on a local scale even for finite, nonperiodic systems, such as lipid nanodiscs. Here we use this computational approach to extract values of K-C and kappa(t) for a set of lipid nanodisc systems that vary in size and lipid composition. We find that the material properties of lipid nanodiscs are different from those of infinite bilayers of corresponding lipid composition, highlighting the effect of nanodisc confinement. Nanodiscs tend to show higher stiffness than their corresponding macroscopic bilayers, and moreover, their material properties vary spatially within them. For small-size MSP1 nanodiscs, the stiffness decreases radially, from a value that is larger in their center than the moduli of the corresponding bilayers by a factor of similar to 2-3. The larger nanodiscs (MSP1E3D1 and MSP2N2) show milder spatial changes of moduli that are composition dependent and can be maximal in the center or at some distance from it. These trends in moduli correlate with spatially varying structural properties, induding the area per lipid and the nanodisc thickness. Finally, as has previously been reported, nanodiscs tend to show deformations from perfectly flat circular geometries to varying degrees, depending on size and lipid composition. The modulations of lipid elastic properties that we find should be carefully considered when making structural and functional inferences concerning embedded proteins.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10102 - Applied mathematics

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2020

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Journal of Physical Chemistry B

ISSN

1520-6106

e-ISSN

—

Svazek periodika

124

Číslo periodika v rámci svazku

33

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

10

Strana od-do

7166-7175

Kód UT WoS článku

000563725900006

EID výsledku v databázi Scopus

2-s2.0-85089768433