Stanford Advisors

All Publications

  • Atomic Recombination in Dynamic Secondary Ion Mass Spectrometry Probes Distance in Lipid Assemblies: A Nanometer Chemical Ruler JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Moss, F. R., Boxer, S. G. 2016; 138 (51): 16737-16744


    The lateral organization of biological membranes is thought to take place on the nanometer length scale. However, this length scale and the dynamic nature of small lipid and protein domains have made characterization of such organization in biological membranes and model systems difficult. Here we introduce a new method for measuring the colocalization of lipids in monolayers and bilayers using stable isotope labeling. We take advantage of a process that occurs in dynamic SIMS called atomic recombination, in which atoms on different molecules combine to form diatomic ions that are detected with a NanoSIMS instrument. This process is highly sensitive to the distance between molecules. By measuring the efficiency of the formation of (13)C(15)N(-) ions from (13)C and (15)N atoms on different lipid molecules, we measure variations in the lateral organization of bilayers even though these heterogeneities occur on a length scale of only a few nm, well below the diameter of the primary ion beam of the NanoSIMS instrument or even the best super-resolution fluorescence methods. Using this technique, we provide direct evidence for nanoscale phase separation in a model membrane, which may provide a better model for the organization of biological membranes than lipid mixtures with microscale phase separation. We expect this technique to be broadly applicable to any assembly where very short scale proximity is of interest or unknown, both in chemical and biological systems.

    View details for DOI 10.1021/jacs.6b10655

    View details for Web of Science ID 000391081800027

    View details for PubMedID 27977192

    View details for PubMedCentralID PMC5287923

  • Dynamic Reorganization and Correlation among Lipid Raft Components. Journal of the American Chemical Society Lozano, M. M., Hovis, J. S., Moss, F. R., Boxer, S. G. 2016; 138 (31): 9996-10001


    Lipid rafts are widely believed to be an essential organizational motif in cell membranes. However, direct evidence for interactions among lipid and/or protein components believed to be associated with rafts is quite limited owing, in part, to the small size and intrinsically dynamic interactions that lead to raft formation. Here, we exploit the single negative charge on the monosialoganglioside GM1, commonly associated with rafts, to create a gradient of GM1 in response to an electric field applied parallel to a patterned supported lipid bilayer. The composition of this gradient is visualized by imaging mass spectrometry using a NanoSIMS. Using this analytical method, added cholesterol and sphingomyelin, both neutral and not themselves displaced by the electric field, are observed to reorganize with GM1. This dynamic reorganization provides direct evidence for an attractive interaction among these raft components into some sort of cluster. At steady state we obtain an estimate for the composition of this cluster.

    View details for DOI 10.1021/jacs.6b05540

    View details for PubMedID 27447959

  • Chemical Synthesis and Self-Assembly of a Ladderane Phospholipid J. Am. Chem. Soc. Mercer, J. A., Cohen, C. M., Shuken, S. R., Wagner, A. M., Smith, M. W., Moss, F. R., Smith, M. D., Vahala, R., Gonzalez-Martinez, A., Boxer, S. G., Burns, N. Z. 2016; 138 (49): 15845–15848

    View details for DOI 10.1021/jacs.6b10706

  • Atomic Recombination in Dynamic Secondary Ion Mass Spectrometry Probes Distance in Lipid Assemblies: A Nanometer Chemical Ruler J. Am. Chem. Soc. Moss, F. R., Boxer, S. G. 2016; 138 (51): 16737–16744

    View details for DOI 10.1021/jacs.6b10655

  • Histone Demethylase LSD1 Is a Folate-Binding Protein BIOCHEMISTRY Luka, Z., Moss, F., Loukachevitch, L. V., Bornhop, D. J., Wagner, C. 2011; 50 (21): 4750-4756


    Methylation of lysine residues in histones has been known to serve a regulatory role in gene expression. Although enzymatic removal of the methyl groups was discovered as early as 1973, the enzymes responsible for their removal were isolated and their mechanism of action was described only recently. The first enzyme to show such activity was LSD1, a flavin-containing enzyme that removes the methyl groups from lysines 4 and 9 of histone 3 with the generation of formaldehyde from the methyl group. This reaction is similar to the previously described demethylation reactions conducted by the enzymes dimethylglycine dehydrogenase and sarcosine dehydrogenase, in which protein-bound tetrahydrofolate serves as an accepter of the formaldehyde that is generated. We now show that nuclear extracts of HeLa cells contain LSD1 that is associated with folate. Using the method of back-scattering interferometry, we have measured the binding of various forms of folate to both full-length LSD1 and a truncated form of LSD1 in free solution. The 6R,S form of the natural pentaglutamate form of tetrahydrofolate bound with the highest affinity (K(d) = 2.8 μM) to full-length LSD1. The fact that folate participates in the enzymatic demethylation of histones provides an opportunity for this micronutrient to play a role in the epigenetic control of gene expression.

    View details for DOI 10.1021/bi200247b

    View details for Web of Science ID 000290837400035

    View details for PubMedID 21510664