PMID- 33329576 OWN - NLM STAT- MEDLINE DCOM- 20210727 LR - 20231110 IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 11 DP - 2020 TI - Maturation of Monocyte-Derived DCs Leads to Increased Cellular Stiffness, Higher Membrane Fluidity, and Changed Lipid Composition. PG - 590121 LID - 10.3389/fimmu.2020.590121 [doi] LID - 590121 AB - Dendritic cells (DCs) are professional antigen-presenting cells of the immune system. Upon sensing pathogenic material in their environment, DCs start to mature, which includes cellular processes, such as antigen uptake, processing and presentation, as well as upregulation of costimulatory molecules and cytokine secretion. During maturation, DCs detach from peripheral tissues, migrate to the nearest lymph node, and find their way into the correct position in the net of the lymph node microenvironment to meet and interact with the respective T cells. We hypothesize that the maturation of DCs is well prepared and optimized leading to processes that alter various cellular characteristics from mechanics and metabolism to membrane properties. Here, we investigated the mechanical properties of monocyte-derived dendritic cells (moDCs) using real-time deformability cytometry to measure cytoskeletal changes and found that mature moDCs were stiffer compared to immature moDCs. These cellular changes likely play an important role in the processes of cell migration and T cell activation. As lipids constitute the building blocks of the plasma membrane, which, during maturation, need to adapt to the environment for migration and DC-T cell interaction, we performed an unbiased high-throughput lipidomics screening to identify the lipidome of moDCs. These analyses revealed that the overall lipid composition was significantly changed during moDC maturation, even implying an increase of storage lipids and differences of the relative abundance of membrane lipids upon maturation. Further, metadata analyses demonstrated that lipid changes were associated with the serum low-density lipoprotein (LDL) and cholesterol levels in the blood of the donors. Finally, using lipid packing imaging we found that the membrane of mature moDCs revealed a higher fluidity compared to immature moDCs. This comprehensive and quantitative characterization of maturation associated changes in moDCs sets the stage for improving their use in clinical application. CI - Copyright (c) 2020 Luhr, Alex, Amon, Krater, Kubankova, Sezgin, Lehmann, Heger, Heidkamp, Smith, Zaburdaev, Bockmann, Levental, Dustin, Eggeling, Guck and Dudziak. FAU - Luhr, Jennifer J AU - Luhr JJ AD - Laboratory of Dendritic Cell Biology, Department of Dermatology, Friedrich-Alexander University Erlangen-Nurnberg (FAU), University Hospital Erlangen, Erlangen, Germany. AD - Nano-Optics, Max-Planck Institute for the Science of Light, Erlangen, Germany. AD - Max-Planck-Zentrum fur Physik und Medizin, Erlangen, Germany. FAU - Alex, Nils AU - Alex N AD - Department of Physics, Friedrich-Alexander University Erlangen-Nurnberg (FAU), Erlangen, Germany. FAU - Amon, Lukas AU - Amon L AD - Laboratory of Dendritic Cell Biology, Department of Dermatology, Friedrich-Alexander University Erlangen-Nurnberg (FAU), University Hospital Erlangen, Erlangen, Germany. FAU - Krater, Martin AU - Krater M AD - Max-Planck-Zentrum fur Physik und Medizin, Erlangen, Germany. AD - Biological Optomechanics, Max-Planck Institute for the Science of Light, Erlangen, Germany. FAU - Kubankova, Marketa AU - Kubankova M AD - Max-Planck-Zentrum fur Physik und Medizin, Erlangen, Germany. AD - Biological Optomechanics, Max-Planck Institute for the Science of Light, Erlangen, Germany. FAU - Sezgin, Erdinc AU - Sezgin E AD - Science for Life Laboratory, Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden. AD - MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Raddcliffe Hospital, University of Oxford, Oxford, United Kingdom. FAU - Lehmann, Christian H K AU - Lehmann CHK AD - Laboratory of Dendritic Cell Biology, Department of Dermatology, Friedrich-Alexander University Erlangen-Nurnberg (FAU), University Hospital Erlangen, Erlangen, Germany. FAU - Heger, Lukas AU - Heger L AD - Laboratory of Dendritic Cell Biology, Department of Dermatology, Friedrich-Alexander University Erlangen-Nurnberg (FAU), University Hospital Erlangen, Erlangen, Germany. FAU - Heidkamp, Gordon F AU - Heidkamp GF AD - Laboratory of Dendritic Cell Biology, Department of Dermatology, Friedrich-Alexander University Erlangen-Nurnberg (FAU), University Hospital Erlangen, Erlangen, Germany. AD - Roche Innovation Center Munich, Roche Pharmaceutical Research and Early Development, pRED, Munich, Germany. FAU - Smith, Ana-Suncana AU - Smith AS AD - PULS Group, Department of Physics, IZNF, Friedrich-Alexander University Erlangen-Nurnberg (FAU), Erlangen, Germany. FAU - Zaburdaev, Vasily AU - Zaburdaev V AD - Max-Planck-Zentrum fur Physik und Medizin, Erlangen, Germany. AD - Mathematics in Life Sciences, Department of Biology, Friedrich-Alexander University Erlangen-Nurnberg (FAU), Erlangen, Germany. AD - Medical Immunology Campus Erlangen, Erlangen, Germany. FAU - Bockmann, Rainer A AU - Bockmann RA AD - Computational Biology, Department of Biology, Friedrich-Alexander University Erlangen-Nurnberg (FAU), Erlangen, Germany. FAU - Levental, Ilya AU - Levental I AD - McGovern Medical School, The University of Texas Health Science Center, Houston, TX, United States. FAU - Dustin, Michael L AU - Dustin ML AD - Kennedy Institute of Rheumatology, University of Oxford, Oxford, United Kingdom. FAU - Eggeling, Christian AU - Eggeling C AD - MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Raddcliffe Hospital, University of Oxford, Oxford, United Kingdom. AD - Institute for Applied Optics and Biophysics, Friedrich-Schiller University Jena, Jena, Germany. AD - Leibniz Institute of Photonic Technologies e.V., Jena, Germany. FAU - Guck, Jochen AU - Guck J AD - Max-Planck-Zentrum fur Physik und Medizin, Erlangen, Germany. AD - Biological Optomechanics, Max-Planck Institute for the Science of Light, Erlangen, Germany. FAU - Dudziak, Diana AU - Dudziak D AD - Laboratory of Dendritic Cell Biology, Department of Dermatology, Friedrich-Alexander University Erlangen-Nurnberg (FAU), University Hospital Erlangen, Erlangen, Germany. AD - Medical Immunology Campus Erlangen, Erlangen, Germany. AD - Deutsches Zentrum Immuntherapie (DZI), Erlangen, Germany. AD - Comprehensive Cancer Center Erlangen-European Metropolitan Area of Nuremberg (CCC ER-EMN), Erlangen, Germany. LA - eng GR - MR/K01577X/1/MRC_/Medical Research Council/United Kingdom GR - 100262Z/12/Z/WT_/Wellcome Trust/United Kingdom GR - BB_/Biotechnology and Biological Sciences Research Council/United Kingdom GR - MC_UU_12025/MRC_/Medical Research Council/United Kingdom GR - MC_UU_00008/9/MRC_/Medical Research Council/United Kingdom GR - 104924/14/Z/14/WT_/Wellcome Trust/United Kingdom GR - MC_UU_12010/9/MRC_/Medical Research Council/United Kingdom GR - MC_UU_12010/MRC_/Medical Research Council/United Kingdom GR - WT_/Wellcome Trust/United Kingdom GR - G0902418/MRC_/Medical Research Council/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20201127 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 SB - IM MH - Cell Differentiation MH - Cells, Cultured MH - Dendritic Cells/*physiology MH - Humans MH - Lipid Metabolism MH - Lipidomics MH - Membrane Fluidity MH - Monocytes/*cytology PMC - PMC7728921 OTO - NOTNLM OT - cell mechanics OT - cellular stiffness OT - cholesterol OT - lipidomics OT - lipids OT - low-density lipoprotein OT - maturation OT - monocyte-derived dendritic cells COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2020/12/18 06:00 MHDA- 2021/07/28 06:00 PMCR- 2020/01/01 CRDT- 2020/12/17 05:50 PHST- 2020/07/31 00:00 [received] PHST- 2020/10/15 00:00 [accepted] PHST- 2020/12/17 05:50 [entrez] PHST- 2020/12/18 06:00 [pubmed] PHST- 2021/07/28 06:00 [medline] PHST- 2020/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2020.590121 [doi] PST - epublish SO - Front Immunol. 2020 Nov 27;11:590121. doi: 10.3389/fimmu.2020.590121. eCollection 2020.