% IMPORTANT: The following is UTF-8 encoded.  This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.

@ARTICLE{Philipp:640496,
      author       = {Philipp, Julian and Sudarsan, Akhil and Kostyurina,
                      Ekaterina and Meklesh, Viktoriia and Berglund, Monica and
                      Rappolt, Michael and Westergren, Jan and Lindfors, Lennart
                      and Schwierz, Nadine and Rädler, Joachim O.},
      title        = {{C}ombining {SAXS} analysis and {MD} simulation to
                      determine structure and hydration of ionizable lipid
                      hexagonal phases},
      journal      = {Soft matter},
      volume       = {21},
      number       = {41},
      issn         = {1744-683X},
      address      = {London},
      publisher    = {Royal Soc. of Chemistry},
      reportid     = {PUBDB-2025-04818},
      pages        = {8049 - 8059},
      year         = {2025},
      abstract     = {Cationic ionizable lipids (CILs) are fundamental components
                      of inverse hexagonal (HII) lipid assemblies, which mediate
                      the encapsulation and release of negatively charged mRNA
                      through a pH-dependent mechanism. Since variations in the
                      structure and composition of the HII phases can
                      significantly impact the biological efficacy of the
                      mRNA-carrying lipid nanoparticles (LNP), a comprehensive
                      understanding of the ionizable lipid HII phases is
                      necessary. We present an integrated approach combining
                      small-angle X-ray scattering (SAXS) experiments, molecular
                      dynamics (MD) simulations and a continuum model to elucidate
                      lipid distribution and water content within HII phases. Our
                      results indicate strong agreement between structures derived
                      from MD simulations and SAXS data. To this end, we introduce
                      a method to correct for periodic boundary artifacts when
                      computing scattering profiles from MD simulations. This
                      enables direct, model-free comparisons between experimental
                      and simulated data, enhancing the reliability of structural
                      interpretations, specifically the water content of the HII
                      phases. Next, we developed a continuum model to extend
                      structural analysis to CIL HII phases for which MD data is
                      unavailable. This integrative framework not only provides
                      molecular-level insights into the ionizable lipid HII
                      mesophase but also enables the prediction of hydration
                      properties across different CIL compositions. The different
                      approaches consistently yield water contents that seem to
                      correlate with the lipids’ transfection efficiencies. By
                      bridging experimental and simulation data, our approach
                      offers a powerful tool for the rational design and
                      optimization of lipid nanoparticles, potentially linking a
                      lower water content with an increased therapeutic
                      performance.},
      cin          = {EMBL-User},
      ddc          = {530},
      cid          = {I:(DE-H253)EMBL-User-20120814},
      pnm          = {6G3 - PETRA III (DESY) (POF4-6G3) / DFG project
                      G:(GEPRIS)440719683 - Hochleistungscompute-Cluster
                      (440719683) / SINE2020 - World class Science and Innovation
                      with Neutrons in Europe 2020 – SINE2020 (654000)},
      pid          = {G:(DE-HGF)POF4-6G3 / G:(GEPRIS)440719683 /
                      G:(EU-Grant)654000},
      experiment   = {EXP:(DE-H253)P-P12-20150101 / EXP:(DE-H253)P-P62-20221101},
      typ          = {PUB:(DE-HGF)16},
      doi          = {10.1039/D5SM00666J},
      url          = {https://bib-pubdb1.desy.de/record/640496},
}