Photo-controlled delivery of very long chain fatty acids to cell membranes and modulation of membrane protein function
| Autor: | Rico J. E. Derks, Frederick Campbell, Edgar Dawkins, Edith Winkler, Li Kong, Frits Kamp, Harald Steiner, Alexander Kros, Martin Giera |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Lipid Bilayers
gamma-Secretase Biochemistry Micelle Polyethylene Glycols Fatty Acids Monounsaturated chemistry.chemical_compound chemistry [Fatty Acids Monounsaturated] 0302 clinical medicine Lipid bilayer Micelles 0303 health sciences biology Chemistry Fatty Acids metabolism [Membrane Lipids] Alzheimer's disease Photochemical Processes Membrane chemistry [Polyethylene Glycols] chemistry [Fatty Acids] Intramembrane protease Biophysics chemistry [Lipid Bilayers] metabolism [Membranes] chemistry [Cell Membrane] Nervonic acid metabolism [Cell Membrane] Light activation Membrane Lipids 03 medical and health sciences Alzheimer Disease ddc:570 Amphiphile Lipidomics isolation & purification [Lipid Bilayers] Humans 030304 developmental biology Membranes Cell Membrane Membrane Proteins Cell Biology Very long chain fatty acids metabolism [Amyloid Precursor Protein Secretases] Cell membranes Membrane protein biology.protein Amyloid Precursor Protein Secretases 030217 neurology & neurosurgery metabolism [Membrane Proteins] |
| Zdroj: | Biochimica et biophysica acta / Biomembranes 1862(5), 183200 (2020). doi:10.1016/j.bbamem.2020.183200 BBA-Biomembranes, 1862(5). ELSEVIER |
| DOI: | 10.1016/j.bbamem.2020.183200 |
| Popis: | The biophysical properties and biological functions of membranes are highly dependent on lipid composition. Supplementing cellular membranes with very long chain fatty acids (vlcFAs) is notoriously difficult given the extreme insolubility of vlcFAs in aqueous solution. Herein, we report a solvent-free, photochemical approach to enrich target membranes with vlcFA. To prevent aggregation of vlcFA, we created light-sensitive micelles composed exclusively of poly-ethylene-glycol-nervonic acid amphiphiles (NA-PEG), which spontaneously disassemble in the presence of lipid bilayers. Once embedded within a membrane, UV light is used to cleave off PEG, leaving free nervonic acid (NA, i.e. FA24:1) in the target membrane. When applied to living cells, free NA was processed by the cell to generate various species of membrane and other lipids with incorporated vlcFAs. In this way, we were able to alter the membrane lipid composition of cellular membranes and modulate the enzymatic activity of gamma-secretase, an intramembrane protease whose dysfunction has been implicated in the onset and progression of Alzheimer's disease. |
| Databáze: | OpenAIRE |
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