TY - JOUR
T1 - Thermal Fluctuations in Amphipol A8-35 Particles
T2 - A Neutron Scattering and Molecular Dynamics Study
AU - Tehei, Moeava
AU - Perlmutter, Jason D.
AU - Giusti, Fabrice
AU - Sachs, Jonathan N.
AU - Zaccai, Giuseppe
AU - Popot, Jean Luc
N1 - Publisher Copyright:
© 2014, Springer Science+Business Media New York.
PY - 2014/10/14
Y1 - 2014/10/14
N2 - Amphipols are a class of polymeric surfactants that can stabilize membrane proteins in aqueous solutions as compared to detergents. A8-35, the best-characterized amphipol to date, is composed of a polyacrylate backbone with ~35 % of the carboxylates free, ~25 % grafted with octyl side-chains, and ~40 % with isopropyl ones. In aqueous solutions, A8-35 self-organizes into globular particles with a molecular mass of ~40 kDa. The thermal dynamics of A8-35 particles was measured by neutron scattering in the 10-picosecond, 18-picosecond, and 1-nanosecond time-scales on natural abundance and deuterium-labeled molecules, which permitted to separate backbone and side-chain motions. A parallel analysis was performed on molecular dynamics trajectories (Perlmutter et al., Langmuir 27:10523–10537, 2011). Experimental results and simulations converge, from their respective time-scales, to show that A8-35 particles feature a more fluid hydrophobic core, predominantly containing the octyl chains, and a more rigid solvent-exposed surface, made up predominantly of the hydrophilic polymer backbone. The fluidity of the core is comparable to that of the lipid environment around proteins in the center of biological membranes, as also measured by neutron scattering. The biological activity of proteins depends sensitively on molecular dynamics, which itself is strongly dependent on the immediate macromolecular environment. In this context, the characterization of A8-35 particle dynamics constitutes a step toward understanding the effect of amphipols on membrane protein stability and function.
AB - Amphipols are a class of polymeric surfactants that can stabilize membrane proteins in aqueous solutions as compared to detergents. A8-35, the best-characterized amphipol to date, is composed of a polyacrylate backbone with ~35 % of the carboxylates free, ~25 % grafted with octyl side-chains, and ~40 % with isopropyl ones. In aqueous solutions, A8-35 self-organizes into globular particles with a molecular mass of ~40 kDa. The thermal dynamics of A8-35 particles was measured by neutron scattering in the 10-picosecond, 18-picosecond, and 1-nanosecond time-scales on natural abundance and deuterium-labeled molecules, which permitted to separate backbone and side-chain motions. A parallel analysis was performed on molecular dynamics trajectories (Perlmutter et al., Langmuir 27:10523–10537, 2011). Experimental results and simulations converge, from their respective time-scales, to show that A8-35 particles feature a more fluid hydrophobic core, predominantly containing the octyl chains, and a more rigid solvent-exposed surface, made up predominantly of the hydrophilic polymer backbone. The fluidity of the core is comparable to that of the lipid environment around proteins in the center of biological membranes, as also measured by neutron scattering. The biological activity of proteins depends sensitively on molecular dynamics, which itself is strongly dependent on the immediate macromolecular environment. In this context, the characterization of A8-35 particle dynamics constitutes a step toward understanding the effect of amphipols on membrane protein stability and function.
KW - Membrane proteins
KW - Molecular dynamics
KW - Polymers
KW - QENS
KW - Surfactants
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U2 - 10.1007/s00232-014-9725-1
DO - 10.1007/s00232-014-9725-1
M3 - Article
C2 - 25204390
AN - SCOPUS:84910124133
SN - 0022-2631
VL - 247
SP - 897
EP - 908
JO - Journal of Membrane Biology
JF - Journal of Membrane Biology
IS - 9-10
ER -