@article{SchulteSoldaSpaenigetal.2022,
  author    = {Schulte, Clemens and Sold{\`a}, Alice and Sp{\"a}nig, Sebastian and Adams, Nathan and Bekić, Ivana and Streicher, Werner and Heider, Dominik and Strasser, Ralf and Maric, Hans Michael},
  title     = {Multivalent binding kinetics resolved by fluorescence proximity sensing},
  series = {Communications Biology},
  volume    = {5},
  journal   = {Communications Biology},
  doi       = {10.1038/s42003-022-03997-3},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-301157},
  year      = {2022},
  abstract  = {Multivalent protein interactors are an attractive modality for probing protein function and exploring novel pharmaceutical strategies. The throughput and precision of state-of-the-art methodologies and workflows for the effective development of multivalent binders is currently limited by surface immobilization, fluorescent labelling and sample consumption. Using the gephyrin protein, the master regulator of the inhibitory synapse, as benchmark, we exemplify the application of Fluorescence proximity sensing (FPS) for the systematic kinetic and thermodynamic optimization of multivalent peptide architectures. High throughput synthesis of +100 peptides with varying combinatorial dimeric, tetrameric, and octameric architectures combined with direct FPS measurements resolved on-rates, off-rates, and dissociation constants with high accuracy and low sample consumption compared to three complementary technologies. The dataset and its machine learning-based analysis deciphered the relationship of specific architectural features and binding kinetics and thereby identified binders with unprecedented protein inhibition capacity; thus, highlighting the value of FPS for the rational engineering of multivalent inhibitors.},
  language  = {en}
}
@article{AueEnglertHarreretal.2023,
  author    = {Aue, Annemarie and Englert, Nils and Harrer, Leon and Schwiering, Fabian and Gaab, Annika and K{\"o}nig, Peter and Adams, Ralf and Schmidtko, Achim and Friebe, Andreas and Groneberg, Dieter},
  title     = {NO-sensitive guanylyl cyclase discriminates pericyte-derived interstitial from intra-alveolar myofibroblasts in murine pulmonary fibrosis},
  series = {Respiratory Research},
  volume    = {24},
  journal   = {Respiratory Research},
  doi       = {10.1186/s12931-023-02479-2},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357805},
  year      = {2023},
  abstract  = {Background The origin of αSMA-positive myofibroblasts, key players within organ fibrosis, is still not fully elucidated. Pericytes have been discussed as myofibroblast progenitors in several organs including the lung. Methods Using tamoxifen-inducible PDGFRβ-tdTomato mice (PDGFRβ-CreERT2; R26tdTomato) lineage of lung pericytes was traced. To induce lung fibrosis, a single orotracheal dose of bleomycin was given. Lung tissue was investigated by immunofluorescence analyses, hydroxyproline collagen assay and RT-qPCR. Results Lineage tracing combined with immunofluorescence for nitric oxide-sensitive guanylyl cyclase (NO-GC) as marker for PDGFRβ-positive pericytes allows differentiating two types of αSMA-expressing myofibroblasts in murine pulmonary fibrosis: (1) interstitial myofibroblasts that localize in the alveolar wall, derive from PDGFRβ+ pericytes, express NO-GC and produce collagen 1. (2) intra-alveolar myofibroblasts which do not derive from pericytes (but express PDGFRβ de novo after injury), are negative for NO-GC, have a large multipolar shape and appear to spread over several alveoli within the injured areas. Moreover, NO-GC expression is reduced during fibrosis, i.e., after pericyte-to-myofibroblast transition. Conclusion In summary, αSMA/PDGFRβ-positive myofibroblasts should not be addressed as a homogeneous target cell type within pulmonary fibrosis.},
  language  = {en}
}