Abstract
The lipid raft hypothesis presents insights into how the cell membrane organizes proteins and lipids to accomplish its many vital functions. Yet basic questions remain about the physical mechanisms that lead to the formation, stability, and size of lipid rafts. As a result, much interest has been generated in the study of systems that contain similar lateral heterogeneities, or domains. In the current work we present an experimental approach that is capable of isolating the bending moduli of lipid domains. This is accomplished using neutron scattering and its unique sensitivity to the isotopes of hydrogen. Combining contrast matching approaches with inelastic neutron scattering, we isolate the bending modulus of 13 nm diameter domains residing in 60 nm unilamellar vesicles, whose lipid composition mimics the mammalian plasma membrane outer leaflet. Importantly, the bending modulus of the nanoscopic domains differs from the modulus of the continuous phase surrounding them. From additional structural measurements and all-atom simulations, we also determine that nanoscopic domains are in-register across the bilayer leaflets. Taken together, these results inform a number of theoretical models of domain/raft formation and highlight the fact that mismatches in bending modulus must be accounted for when explaining the emergence of lateral heterogeneities in lipid systems and biological membranes.
Original language | English |
---|---|
Pages (from-to) | 15772-15780 |
Number of pages | 9 |
Journal | Journal of the American Chemical Society |
Volume | 137 |
Issue number | 50 |
DOIs | |
State | Published - Dec 23 2015 |
Funding
The authors gratefully acknowledge Professors F. Brown, R. Epand, G.W. Feigenson, and M. Schick for a critical reading of the manuscript and insightful conversations; J. Neuefeind, C. Gao, R. Moody, M. Doktorova, M. Cochran, and P. Zolnierczuk for technical assistance; and Prof. H. Riezman (Univ. of Geneva) for the generous gift of cholesterolproducing yeast strain and protocol. JDN is partially supported by the U.S. DOE BES through the EPSCoR Grant No. DEFG02- 08ER46528. JK is supported through the Scientific User Facilities Division of the DOE Office of Basic Energy Sciences (BES), under contract no. DE-AC05 00OR2275. XC is partially supported by the Laboratory Directed R&D (LDRD) fund P7394 at the Oak Ridge National Laboratory. This research used resources of the Oak Ridge Leadership Computing Facility at the Oak Ridge National Laboratory, which is supported by the Office of Science of the U.S. Department of Energy under Contract No. DE-AC05-00OR22725. Research conducted at ORNL’s Spallation Neutron Source was sponsored by the Scientific User Facilities Division, Office of Basic Energy Sciences, US Department of Energy. Oak Ridge National Laboratory is managed by UT-Battelle, LLC under US DOE Contract No. DE-AC05-00OR22725.