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Title: Designing Mixed Detergent Micelles for Uniform Neutron Contrast

Micelle-forming detergents provide an amphipathic environment that mimics lipid bilayers and are important tools used to solubilize and stabilize membrane proteins in solution for in vitro structural investigations. Small-angle neutron scattering (SANS) performed at the neutron contrast match point of detergent molecules allows observing the scattering signal from membrane proteins unobstructed by contributions from the detergent. However, we show here that even for a perfectly average-contrast matched detergent there arises significant core-shell scattering from the contrast difference between aliphatic detergent tails and hydrophilic head groups. This residual signal at the average detergent contrast match point interferes with interpreting structural data of membrane proteins. This complication is often made worse by the presence of excess empty (protein-free) micelles. Here, we present an approach for the rational design of mixed micelles containing a deuterated detergent analog, which eliminates neutron contrast between core and shell, and allows the micelle scattering to be fully contrast matched to unambiguously resolve membrane protein structure using solution SANS.
Authors:
ORCiD logo [1] ; ORCiD logo [1] ; ORCiD logo [1]
  1. Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
Publication Date:
Grant/Contract Number:
AC05-00OR22725
Type:
Accepted Manuscript
Journal Name:
Journal of Physical Chemistry Letters
Additional Journal Information:
Journal Volume: 8; Journal Issue: 20; Journal ID: ISSN 1948-7185
Publisher:
American Chemical Society
Research Org:
Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
Sponsoring Org:
USDOE Office of Science (SC)
Country of Publication:
United States
Language:
English
Subject:
37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; 59 BASIC BIOLOGICAL SCIENCES
OSTI Identifier:
1407776

Oliver, Ryan C., Pingali, Sai Venkatesh, and Urban, Volker S.. Designing Mixed Detergent Micelles for Uniform Neutron Contrast. United States: N. p., Web. doi:10.1021/acs.jpclett.7b02149.
Oliver, Ryan C., Pingali, Sai Venkatesh, & Urban, Volker S.. Designing Mixed Detergent Micelles for Uniform Neutron Contrast. United States. doi:10.1021/acs.jpclett.7b02149.
Oliver, Ryan C., Pingali, Sai Venkatesh, and Urban, Volker S.. 2017. "Designing Mixed Detergent Micelles for Uniform Neutron Contrast". United States. doi:10.1021/acs.jpclett.7b02149. https://www.osti.gov/servlets/purl/1407776.
@article{osti_1407776,
title = {Designing Mixed Detergent Micelles for Uniform Neutron Contrast},
author = {Oliver, Ryan C. and Pingali, Sai Venkatesh and Urban, Volker S.},
abstractNote = {Micelle-forming detergents provide an amphipathic environment that mimics lipid bilayers and are important tools used to solubilize and stabilize membrane proteins in solution for in vitro structural investigations. Small-angle neutron scattering (SANS) performed at the neutron contrast match point of detergent molecules allows observing the scattering signal from membrane proteins unobstructed by contributions from the detergent. However, we show here that even for a perfectly average-contrast matched detergent there arises significant core-shell scattering from the contrast difference between aliphatic detergent tails and hydrophilic head groups. This residual signal at the average detergent contrast match point interferes with interpreting structural data of membrane proteins. This complication is often made worse by the presence of excess empty (protein-free) micelles. Here, we present an approach for the rational design of mixed micelles containing a deuterated detergent analog, which eliminates neutron contrast between core and shell, and allows the micelle scattering to be fully contrast matched to unambiguously resolve membrane protein structure using solution SANS.},
doi = {10.1021/acs.jpclett.7b02149},
journal = {Journal of Physical Chemistry Letters},
number = 20,
volume = 8,
place = {United States},
year = {2017},
month = {9}
}