Interfacial Interactions of Nanoparticles and Molecular Nanostructures with Model Membrane Systems

A special issue of Membranes (ISSN 2077-0375). This special issue belongs to the section "Biological Membranes".

Deadline for manuscript submissions: closed (30 November 2025) | Viewed by 4880

Special Issue Editor


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Guest Editor
Department of Physical Chemistry, Faculty of Chemistry and Pharmacy, Sofia University, St. Kliment Ohridsk, Sofia 1164, Bulgaria
Interests: biophysics; medical physics; soft matter; atomic force microscopy (AFM); Langmuir monolayers; lipid bilayers; nanoparticles and nanostructured materials; enzyme reactions; influence of ionizing radiation on biologically important molecules and structures
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Special Issue Information

Dear Colleagues,

Ever since Singer and Nicolson introduced the membrane model over half a century ago, the complex structural organization of the cell membrane has been hinted at, including its lipid heterogeneity, asymmetry, and the presence of integral, peripheral, and other proteins embedded within its structure. From that time to the present day, studying cell membranes and developing adequate molecular models that mimic their structure and functions have remained some of the most significant challenges in biophysical science.

Theoretical and experimental approaches have driven progress in understanding and interpreting the physicochemical properties governing these processes. Simplified model membrane systems have been proposed that reveal the nature of the interactions of various molecular structures with cell membranes at the nanoscale level. The most commonly used and well-known model membrane systems include monolayers, bilayers, liposomes, and membranes formed on solid substrates, such as Langmuir–Blodgett (LB) films. These systems imitate the lipid composition, curvature, domains, rafts, and physicochemical properties of cellular membranes.

Over the years, technological progress has led to the development of numerous sensitive experimental methods applicable to liquid surfaces, such as atomic force microscopy, fluorescence microscopy, Brewster angle microscopy, X-ray and neutron scattering, ellipsometry, FTIR spectroscopy, and nonlinear optical spectroscopy. Combined with new, more powerful computational methods, these advancements have created opportunities for us to understand the changes that occur in cell membranes when they interact with nanoparticles, enzymes, other macromolecules, or drug formulations. These interactions involve chemical reactions or processes at their interfaces, leading to reorganization and changes in membrane structure.

In light of the above, this Special Issue aims to provide an opportunity for researchers working in the aforementioned scientific fields to publish original research articles, comprehensive reviews, and short communications focused on aspects of the interactions between model membrane systems (monolayers, bilayers, liposomes, LB films, etc.) and nanoscale structures (nanoparticles, molecularly organized structures, enzymes, macromolecules, etc.). We hope that with the combined efforts of scientists from various fields of the life and physical sciences, new horizons will open in the study and understanding of vital phenomena related to the structure and molecular organization of cell membranes.

Prof. Dr. Konstantin T. Balashev
Guest Editor

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Keywords

  • monolayers
  • bilayers
  • liposomes
  • atomic force microscopy (AFM)
  • fluorescence microscopy
  • X-ray and neutron scattering
  • nanoparticles
  • macromolecules
  • enzymes
  • protein–lipid interactions

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Published Papers (3 papers)

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Research

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15 pages, 1801 KB  
Article
Bacterial Nanocellulose Functionalized with Graphite and Niobium Pentoxide: Limited Antimicrobial Effects and Preserved Cytocompatibility
by Juliana Silva Ribeiro de Andrade, Adriana Poli Castilho Dugaich, Andressa da Silva Barboza, Maurício Malheiros Badaró, Pedro Henrique Santaliestra e Silva, Tiago Moreira Bastos Campos, Karina Cesca, Debora de Oliveira, Sheila Cristina Stolf and Rafael Guerra Lund
Membranes 2026, 16(1), 16; https://doi.org/10.3390/membranes16010016 - 31 Dec 2025
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Abstract
Chronic wounds remain locked in persistent inflammation with high microbial burden, demanding dressings that suppress infection without sacrificing biocompatibility. Bacterial nanocellulose (BNC) is an attractive matrix due to its biocompatibility, nanofibrillar architecture, and moisture retention, but it lacks antimicrobial activity. Here, we engineer [...] Read more.
Chronic wounds remain locked in persistent inflammation with high microbial burden, demanding dressings that suppress infection without sacrificing biocompatibility. Bacterial nanocellulose (BNC) is an attractive matrix due to its biocompatibility, nanofibrillar architecture, and moisture retention, but it lacks antimicrobial activity. Here, we engineer BNC membranes post-functionalized with functionalized graphite (f-Gr; predominantly graphitic with residual surface groups) and/or niobium pentoxide (Nb2O5), and evaluate four groups: BNC (matrix control), BNC/Nb2O5, BNC/f-Gr, and BNC/f-Gr/Nb2O5. Physicochemical analyses (Raman and Voigt fitting, FTIR-ATR, XRD, and SEM) confirm a graphitic carbon phase and physical incorporation of the modifiers into the BNC network, with a noticeable shift in the hydration/polarity profile—more evident in the presence of f-Gr. In standardized microbiological assays, BNC/f-Gr promoted a moderate, contact-dependent reduction in bacterial proliferation, particularly against Staphylococcus aureus, whereas BNC/Nb2O5 behaved similarly to pristine BNC under the tested conditions. The combined f-Gr/Nb2O5 formulation showed an intermediate antimicrobial response, with no clear synergy beyond f-Gr alone. Cytotoxicity assays indicated cytocompatibility for BNC, BNC/f-Gr, and BNC/Nb2O5; the combined group displayed a slight reduction that remained within acceptable limits. Overall, BNC/f-Gr emerges as the most promising antimicrobial dressing, while Nb2O5 did not significantly enhance antimicrobial performance under the tested conditions and warrants further optimization regarding loading and distribution. Full article
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Review

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40 pages, 13676 KB  
Review
Interfacial Interactions of Nanoparticles and Molecular Nanostructures with Model Membrane Systems: Mechanisms, Methods, and Applications
by Konstantin Balashev
Membranes 2026, 16(4), 134; https://doi.org/10.3390/membranes16040134 - 1 Apr 2026
Viewed by 1685
Abstract
This review surveys how nanoparticles and biomolecular nanosized structures interact with model membrane systems, and how these interfacial processes govern their performance in drug and gene delivery, antimicrobial strategies, biosensing, and nanotoxicology. The nanostructures covered include polymeric nanoparticles, lipid-based carriers, peptide nanostructures, dendrimers, [...] Read more.
This review surveys how nanoparticles and biomolecular nanosized structures interact with model membrane systems, and how these interfacial processes govern their performance in drug and gene delivery, antimicrobial strategies, biosensing, and nanotoxicology. The nanostructures covered include polymeric nanoparticles, lipid-based carriers, peptide nanostructures, dendrimers, and multifunctional hybrids. Model membranes span Langmuir monolayers, supported lipid bilayers, vesicles/liposomes across sizes, and emerging hybrid or asymmetric constructs that better approximate native complexity. Mechanistically, interactions follow recurrent routes—surface adsorption, bilayer insertion, pore formation, and lipid extraction/reorganization—regulated by particle size, morphology, charge, ligand architecture, and lipophilicity, in conjunction with membrane composition, phase state, curvature, and asymmetry. A multiscale toolkit links structure, mechanics, and dynamics: Langmuir troughs and Brewster Angle Microscopy map thermodynamics and mesoscale morphology; atomic force microscopy and quartz crystal microbalance with dissipation resolve nanoscale topography and viscoelasticity; fluorescence microscopy/spectroscopy reports on localization and packing; neutron and X-ray reflectometry quantify vertical structure; molecular dynamics provides atomistic pathways and design hypotheses. Historically, the field advanced from early monolayers and bilayers, through the fluid mosaic model, to raft microdomains and modern biomimetic systems, enabling increasingly realistic experiments. Key advances include cross-method integration linking experimental observations with image-based computational models; persistent debates concern the translation from simplified models to living membranes, the role of dynamic coronas, and scale/force-field limits in simulations. Future efforts should prioritize hybrid models incorporating proteins and asymmetric lipidomes, standardized reporting and reference systems, rigorous coupling of experiments with calibrated simulations and machine learning, and alignment with safety-by-design and regulatory expectations, thereby shifting interfacial measurements from descriptive observation to predictive design rules. Full article
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22 pages, 5738 KB  
Review
Probing Membrane Structure of Lipid Nanomedicines Using Solution Small-Angle X-Ray Scattering: Applications and Prospects
by Ke-Meng Li, Panqi Song, Xiao-Peng He and Na Li
Membranes 2025, 15(12), 382; https://doi.org/10.3390/membranes15120382 - 16 Dec 2025
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Abstract
Lipid-based nanomedicines are already widely used in antitumor therapy and gene delivery. However, their complex structural features demand advanced mesoscopic structural characterization tools for effective research and development (R&D) and quality control. Synchrotron small-angle X-ray scattering (SAXS) is a powerful, non-invasive technique for [...] Read more.
Lipid-based nanomedicines are already widely used in antitumor therapy and gene delivery. However, their complex structural features demand advanced mesoscopic structural characterization tools for effective research and development (R&D) and quality control. Synchrotron small-angle X-ray scattering (SAXS) is a powerful, non-invasive technique for probing nanoscale membrane organizations, monitoring in situ dynamic membrane assembly, and exploring the interactions of components in lipid-based drug delivery systems, including liposomes, lipoplexes, lipid nanoparticles (LNPs), and lyotropic liquid crystals (LLCs). Recent advances in high-flux synchrotron facilities, high-frequency detectors, and automated SAXS data processing pipelines permit a detailed structural characterization of lamellarity, bilayer spacing, internal phases, core–shell morphology, as well as “pump-probe” dynamic process studies for lipid nanomedicines. Though major challenges remain in sample polydispersity and model fitting, the advances in time-resolved synchrotron SAXS, high-throughput automation, and artificial intelligence (AI)-assisted modeling are rapidly reducing this barrier. This review summarizes SAXS methodology and introduces representative case studies in the field of lipid nanomedicines. The performance of BioSAXS beamline BL19U2 in the Shanghai synchrotron radiation facility (SSRF) and prospects of AI-guided drug screening at BL19U2 are highlighted to advance intelligent R&D and quality control for lipid nanomedicines. Full article
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