DOI: https://doi.org/10.14710/jpa.v8i3.31465

Composition-Dependent Structural and Dynamical Properties of Mixed DPPC/DLPC Bilayers: An Atomistic Molecular Dynamics Study

*Gregoria Illya orcid scopus  -  Physics Department, Matana University, Tangerang, Indonesia, Indonesia
Hadi Sutanto orcid scopus  -  Atma Jaya Catholic University of Indonesia, Department of Mechanical Engineering, Jakarta, Indonesia, Indonesia
Received: 28 Feb 2026; Revised: 23 Jul 2026; Accepted: 3 Aug 2026; Available online: 31 Aug 2026; Published: 31 Aug 2026.

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Abstract

Moderate chain-length mismatch in saturated lipid mixtures provides a useful model for understanding how structural perturbations influence membrane behavior. Here, all-atom molecular dynamics simulations were used to investigate DPPC/DLPC bilayers across compositions at 50 °C, focusing on the coupled evolution of structure, dynamics, and hydration. Increasing DLPC content leads to a systematic increase in area per lipid and a reduction in bilayer thickness, indicating weakened packing within the hydrophobic core. These structural changes are accompanied by enhanced interleaflet coupling and decreased acyl-chain ordering. The lateral diffusion behavior is composition-dependent: DLPC mobility increases steadily with concentration, whereas DPPC exhibits a non-monotonic trend, reflecting competing effects of increased free volume and heterogeneous packing. Mean squared displacement analysis in log–log representation reveals persistent subdiffusive dynamics for both lipid species, with diffusion exponents α ≈ 0.30–0.35 across all compositions. This indicates that lipid motion remains governed by transient confinement and spatial heterogeneity, even as overall mobility increases. In parallel, water density profiles show enhanced penetration of water into the bilayer interior with increasing DLPC fraction, driven by packing defects and increased free volume rather than pore formation. These results demonstrate that moderate chain-length mismatch induces a coupled structural and dynamical response that governs membrane transport properties.

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Keywords: Molecular dynamics simulation; Phospholipid mixture; Biological membrane; Lipid interdigitation; Hydrophobic mismatch
Funding: Matana University

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  1. S. J. Marrink, V. Corradi, P. C. Tieleman, D. P. Tieleman, and H. J. C. Berendsen, “Computational modeling of realistic cell membranes,” Chem. Rev. 119, 6184–6226 (2019)
  2. R. Friedman, M. Khalid, and O. Beckstein, “Understanding conformational dynamics of complex lipid mixtures relevant to biology,” J. Membr. Biol. 251, 609–631 (2018)
  3. W. Ding, J. Palaiokostas, and R. Faller, “Effects of lipid composition on bilayer membranes quantified by all-atom molecular dynamics,” J. Phys. Chem. B 119, 15263–15274 (2015)
  4. A. H. Poghosyan, H. H. Gharabekyan, and A. A. Shahinyan, “Molecular dynamics simulations of DMPC/DPPC mixed bilayers,” Int. J. Mod. Phys. C 18, 73–89 (2007)
  5. P. S. Coppock and J. T. Kindt, “Atomistic simulations of mixed-lipid bilayers in gel and fluid phases,” Langmuir 25, 352–359 (2008)
  6. B. Y. Wong and R. Faller, “Phase behavior and dynamic heterogeneities in lipids,” Biochim. Biophys. Acta Biomembr. 1768, 620–627 (2007)
  7. G. Illya, R. Lipowsky, and J. C. Shillcock, “Effect of chain length and asymmetry on material properties of bilayer membranes,” J. Chem. Phys. 122, 244901 (2005)
  8. J. Xu, Y. Zhang, H. Liu, X. Chen, and W. Wang, “Understanding the mechanical properties of ultradeformable liposomes using molecular dynamics simulations,” J. Phys. Chem. B 127, 9496–9512 (2023)
  9. R. M. Venable, F. L. H. Brown, and R. W. Pastor, “Molecular dynamics simulations of membrane permeability,” Chem. Rev. 119, 5954–5997 (2019)
  10. J. Frallicciardi, J. Melcr, P. Siginou, S. J. Marrink, and B. Poolman, “Membrane thickness, lipid phase and sterol type are determining factors in the permeability of membranes to small solutes,” Nat. Commun. 13, 1605 (2022)
  11. T. Róg and I. Vattulainen, “Lipid membranes: theory and simulations bridged to experiments,” Biochim. Biophys. Acta Biomembr. 1858, 2251–2253 (2016)
  12. H. Hashemzadeh, H. Javadi, and M. H. Darvishi, “Study of structural stability and formation mechanisms in DSPC and DPSM liposomes,” Sci. Rep. 10, 1837 (2020)
  13. G. Illya, “A diffusion-based model of doxorubicin release from liposomes,” Buletin Fisika 26, 222–230 (2025)
  14. S. Jo, T. Kim, V. G. Iyer, and W. Im, “CHARMM-GUI: A web-based graphical user interface for CHARMM,” J. Comput. Chem. 29, 1859–1865 (2008)
  15. B. R. Brooks, C. L. Brooks III, A. D. MacKerell Jr., L. Nilsson, R. J. Petrella, B. Roux, Y. Won, G. Archontis, C. Bartels, S. Boresch, A. Caflisch, L. Caves, Q. Cui, A. R. Dinner, M. Feig, S. Fischer, J. Gao, M. Hodoscek, W. Im, K. Kuczera, T. Lazaridis, J. Ma, V. Ovchinnikov, E. Paci, R. W. Pastor, C. B. Post, J. Z. Pu, M. Schaefer, B. Tidor, R. M. Venable, H. L. Woodcock, X. Wu, W. Yang, D. M. York, and M. Karplus, “CHARMM: The biomolecular simulation program,” J. Comput. Chem. 30, 1545–1614 (2009)
  16. J. Lee, X. Cheng, J. M. Swails, M. S. Yeom, P. K. Eastman, J. A. Lemkul, S. Wei, J. Buckner, J. C. Jeong, Y. Qi, S. Jo, V. S. Pande, D. A. Case, C. L. Brooks III, A. D. MacKerell Jr., J. B. Klauda, and W. Im, “CHARMM-GUI input generator for NAMD, GROMACS, AMBER, OpenMM, and CHARMM/OpenMM simulations using the CHARMM36 additive force field,” J. Chem. Theory Comput. 12, 405–413 (2016)
  17. A. D. MacKerell Jr., D. Bashford, M. Bellott, R. L. Dunbrack Jr., J. D. Evanseck, M. J. Field, S. Fischer, J. Gao, H. Guo, S. Ha, D. Joseph-McCarthy, L. Kuchnir, K. Kuczera, F. T. K. Lau, C. Mattos, S. Michnick, T. Ngo, D. T. Nguyen, B. Prodhom, W. E. Reiher III, B. Roux, M. Schlenkrich, J. C. Smith, R. Stote, J. Straub, M. Watanabe, J. Wiórkiewicz-Kuczera, D. Yin, and M. Karplus, “All-atom empirical potential for molecular modeling and dynamics studies of proteins,” J. Phys. Chem. B 102, 3586–3616 (1998)
  18. J. B. Klauda, R. M. Venable, J. A. Freites, J. W. O’Connor, D. J. Tobias, C. Mondragon-Ramirez, I. Vorobyov, A. D. MacKerell Jr., and R. W. Pastor, “Update of the CHARMM all-atom additive force field for lipids: Validation on six lipid types,” J. Phys. Chem. B 114, 7830–7843 (2010)
  19. R. W. Pastor and A. D. MacKerell Jr., “Development of the CHARMM force field for lipids,” J. Phys. Chem. Lett. 2, 1526–1532 (2011)
  20. W. L. Jorgensen, J. Chandrasekhar, J. D. Madura, R. W. Impey, and M. L. Klein, “Comparison of simple potential functions for simulating liquid water,” J. Chem. Phys. 79, 926–935 (1983)
  21. M. J. Abraham, T. Murtola, R. Schulz, S. Páll, J. C. Smith, B. Hess, and E. Lindahl, “GROMACS: High performance molecular simulations through multi-level parallelism from laptops to supercomputers,” SoftwareX 1–2, 19–25 (2015)
  22. D. van der Spoel, E. Lindahl, B. Hess, G. Groenhof, A. E. Mark, and H. J. C. Berendsen, “GROMACS: Fast, flexible, and free,” J. Comput. Chem. 26, 1701–1718 (2005)
  23. S. Pronk, S. Páll, R. Schulz, P. Larsson, P. Bjelkmar, R. Apostolov, M. R. Shirts, J. C. Smith, P. M. Kasson, D. van der Spoel, B. Hess, and E. Lindahl, “GROMACS 4.5: A high-throughput and highly parallel open source molecular simulation toolkit,” Bioinformatics 29, 845–854 (2013)
  24. G. Bussi, D. Donadio, and M. Parrinello, “Canonical sampling through velocity rescaling,” J. Chem. Phys. 126, 014101 (2007)
  25. M. Parrinello and A. Rahman, “Polymorphic transitions in single crystals: A new molecular dynamics method,” J. Appl. Phys. 52, 7182–7190 (1981)
  26. U. Essmann, L. Perera, M. L. Berkowitz, T. Darden, H. Lee, and L. G. Pedersen, “A smooth particle mesh Ewald method,” J. Chem. Phys. 103, 8577–8593 (1995)
  27. B. Hess, H. Bekker, H. J. C. Berendsen, and J. G. E. M. Fraaije, “LINCS: A linear constraint solver for molecular simulations,” J. Comput. Chem. 18, 1463–1472 (1997)
  28. J. F. Nagle and S. Tristram-Nagle, “Structure of lipid bilayers,” Biochim. Biophys. Acta 1469, 159–195 (2000)
  29. J. F. Nagle and S. Tristram-Nagle, “Lipid bilayer structure,” Curr. Opin. Struct. Biol. 10, 474–480 (2000)
  30. J. F. Nagle, R. Zhang, S. Tristram-Nagle, W. Sun, H. I. Petrache, and R. M. Suter, “X-ray structure determination of fully hydrated lipid bilayers,” Biophys. J. 70, 1419–1431 (1996)
  31. N. Kučerka, M.-P. Nieh, and J. Katsaras, “Fluid phase lipid areas and bilayer thicknesses of commonly used phosphatidylcholines as a function of temperature,” Biochim. Biophys. Acta Biomembr. 1808, 2761–2771 (2011)
  32. N. Kučerka, S. Tristram-Nagle, and J. F. Nagle, “Structure of fully hydrated fluid phase lipid bilayers with monounsaturated chains,” J. Membr. Biol. 208, 193–202 (2006)
  33. U. Essmann and M. L. Berkowitz, “Dynamical properties of phospholipid bilayers from computer simulation,” Biophys. J. 76, 2081–2089 (1999)
  34. J. Repáková, J. M. Holopainen, M. R. Morrow, M. C. McDonald, P. Capková, and I. Vattulainen, “Influence of DPH on the structure and dynamics of a DPPC bilayer,” Biophys. J. 88, 3398–3410 (2005)
  35. J. Frallicciardi, J. Melcr, P. Siginou, et al., “Membrane thickness, lipid phase and sterol type are determining factors in the permeability of membranes to small solutes,” Nat. Commun. 13, 1605 (2022)

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