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Membranes
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Nanotechnologies and Nanoparticles Interaction with Bio-Membranes
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Nanotechnologies and Nanoparticles Interaction with Bio-Membranes

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

Deadline for manuscript submissions: closed (30 November 2023) | Viewed by 13492

Special Issue Editors

Dr. Andrea Mescola

E-Mail Website
Guest Editor
Istituto Nanoscienze, Consiglio Nazionale delle Ricerche (CNR-Nano S3-Modena), Via G.Campi 213/A, 41125 Modena, Italy
Interests: nanotechnology; surface functionalization; lipid bilayers; liposomes; atomic force microscopy; force spectroscopy; friction force microscopy; optical microscopy; biophysics; physical chemistry; nanomedicine; sensors; biomaterials; smart surfaces; antimicrobial peptides; single-molecule techniques; nanomechanical characterization; 2D materials
Dr. Dhawal Choudhary

E-Mail Website
Guest Editor
The Tans Lab, AMOLF, Amsterdam, The Netherlands
Interests: biophysics; biosystems; optical tweezers; biomolecules; proteins; single-molecule force spectroscopy; molecular chaperones; protein–protein interactions; protein folding

Special Issue Information

Dear Colleagues, 

The ever-evolving world of nanotechnology has spurred a new era of biosystems investigated from a nanoperspective. Nanotechnology approaches, in particular nanoparticles have been effectively used for a wide range of biomedical applications such as phototherapy, cell imaging, inducing or prevention of mutations, modulation of cellular conformation, drug/gene delivery, and so on. Among numerous biosystems, biomembranes have emerged as a special interest in this bio-nano revolution. Biomembranes provide a diverse array of interacting partners to nanoparticles and/or to relevant exogenous molecules. Nanotechnology can be employed to manipulate the functionality and structure of biomembranes as well as fabricate synthetic counterparts, which opens further avenues. The field at present boasts an impressive array of theoretical, computational, and experimental work being carried out worldwide, further pushing the envelope. Numerous challenges still exist in this sphere, and an improvement in the understanding of nanoparticle-biosystem interactions and further development in experimental approaches promises a bright future.

Dr. Mescola Andrea
Dr. Dhawal Choudhary
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Membranes is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • nanoparticles
  • biomembranes
  • biosystems
  • nanotechnology
  • biomolecular organization
  • lipid interaction
  • model membranes
  • liposomes
  • vesicles

Published Papers (7 papers)

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Research

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21 pages, 5993 KiB  
Article
Bioinspired Nanoplatforms Based on Graphene Oxide and Neurotrophin-Mimicking Peptides
by Luigi Redigolo, Vanessa Sanfilippo, Diego La Mendola, Giuseppe Forte and Cristina Satriano
Membranes 2023, 13(5), 489; https://doi.org/10.3390/membranes13050489 - 30 Apr 2023
Cited by 2 | Viewed by 1710
Abstract
Neurotrophins (NTs), which are crucial for the functioning of the nervous system, are also known to regulate vascularization. Graphene-based materials may drive neural growth and differentiation, and, thus, have great potential in regenerative medicine. In this work, we scrutinized the nano–biointerface between the [...] Read more.
Neurotrophins (NTs), which are crucial for the functioning of the nervous system, are also known to regulate vascularization. Graphene-based materials may drive neural growth and differentiation, and, thus, have great potential in regenerative medicine. In this work, we scrutinized the nano–biointerface between the cell membrane and hybrids made of neurotrophin-mimicking peptides and graphene oxide (GO) assemblies (pep−GO), to exploit their potential in theranostics (i.e., therapy and imaging/diagnostics) for targeting neurodegenerative diseases (ND) as well as angiogenesis. The pep−GO systems were assembled via spontaneous physisorption onto GO nanosheets of the peptide sequences BDNF(1-12), NT3(1-13), and NGF(1-14), mimicking the brain-derived neurotrophic factor (BDNF), the neurotrophin 3 (NT3), and the nerve growth factor (NGF), respectively. The interaction of pep−GO nanoplatforms at the biointerface with artificial cell membranes was scrutinized both in 3D and 2D by utilizing model phospholipids self-assembled as small unilamellar vesicles (SUVs) or planar-supported lipid bilayers (SLBs), respectively. The experimental studies were paralleled via molecular dynamics (MD) computational analyses. Proof-of-work in vitro cellular experiments with undifferentiated neuroblastoma (SH-SY5Y), neuron-like, differentiated neuroblastoma (dSH-SY5Y), and human umbilical vein endothelial cells (HUVECs) were carried out to shed light on the capability of the pep−GO nanoplatforms to stimulate the neurite outgrowth as well as tubulogenesis and cell migration. Full article
(This article belongs to the Special Issue Nanotechnologies and Nanoparticles Interaction with Bio-Membranes)
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11 pages, 2362 KiB  
Article
Lipoprotein Particles as Shuttles for Hydrophilic Cargo
by Florian Weber, Markus Axmann, Andreas Horner, Bettina Schwarzinger, Julian Weghuber and Birgit Plochberger
Membranes 2023, 13(5), 471; https://doi.org/10.3390/membranes13050471 - 28 Apr 2023
Viewed by 1000
Abstract
Lipoprotein particles (LPs) are excellent transporters and have been intensively studied in cardiovascular diseases, especially regarding parameters such as their class distribution and accumulation, site-specific delivery, cellular internalization, and escape from endo/lysosomal compartments. The aim of the present work is the hydrophilic cargo [...] Read more.
Lipoprotein particles (LPs) are excellent transporters and have been intensively studied in cardiovascular diseases, especially regarding parameters such as their class distribution and accumulation, site-specific delivery, cellular internalization, and escape from endo/lysosomal compartments. The aim of the present work is the hydrophilic cargo loading of LPs. As an exemplary proof-of-principle showcase, the glucose metabolism-regulating hormone, insulin, was successfully incorporated into high-density lipoprotein (HDL) particles. The incorporation was studied and verified to be successful using Atomic Force Microscopy (AFM) and Fluorescence Microscopy (FM). Single-molecule-sensitive FM together with confocal imaging visualized the membrane interaction of single, insulin-loaded HDL particles and the subsequent cellular translocation of glucose transporter type 4 (Glut4). Full article
(This article belongs to the Special Issue Nanotechnologies and Nanoparticles Interaction with Bio-Membranes)
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18 pages, 4160 KiB  
Article
Biomechanical Role of Epsin in Influenza A Virus Entry
by Jophin G. Joseph, Rajat Mudgal, Shan-Shan Lin, Akira Ono and Allen P. Liu
Membranes 2022, 12(9), 859; https://doi.org/10.3390/membranes12090859 - 05 Sep 2022
Cited by 3 | Viewed by 2037
Abstract
Influenza A virus (IAV) utilizes clathrin-mediated endocytosis for cellular entry. Membrane-bending protein epsin is a cargo-specific adaptor for IAV entry. Epsin interacts with ubiquitinated surface receptors bound to IAVs via its ubiquitin interacting motifs (UIMs). Recently, epsin was shown to have membrane tension [...] Read more.
Influenza A virus (IAV) utilizes clathrin-mediated endocytosis for cellular entry. Membrane-bending protein epsin is a cargo-specific adaptor for IAV entry. Epsin interacts with ubiquitinated surface receptors bound to IAVs via its ubiquitin interacting motifs (UIMs). Recently, epsin was shown to have membrane tension sensitivity via its amphiphilic H0 helix. We hypothesize this feature is important as IAV membrane binding would bend the membrane and clinical isolates of IAVs contain filamentous IAVs that may involve more membrane bending. However, it is not known if IAV internalization might also depend on epsin’s H0 helix. We found that CALM, a structurally similar protein to epsin lacking UIMs shows weaker recruitment to IAV-containing clathrin-coated structures (CCSs) compared to epsin. Removal of the ENTH domain of epsin containing the N-terminus H0 helix, which detects changes in membrane curvature and membrane tension, or mutations in the ENTH domain preventing the formation of H0 helix reduce the ability of epsin to be recruited to IAV-containing CCSs, thereby reducing the internalization of spherical IAVs. However, internalization of IAVs competent in filamentous particle formation is not affected by the inhibition of H0 helix formation in the ENTH domain of epsin. Together, these findings support the hypothesis that epsin plays a biomechanical role in IAV entry. Full article
(This article belongs to the Special Issue Nanotechnologies and Nanoparticles Interaction with Bio-Membranes)
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15 pages, 1580 KiB  
Article
Interaction of Bortezomib with Cell Membranes Regulates Its Toxicity and Resistance to Therapy
by Maria João Ramalho, Stéphanie Andrade, Joana Angélica Loureiro and Maria Carmo Pereira
Membranes 2022, 12(9), 823; https://doi.org/10.3390/membranes12090823 - 23 Aug 2022
Cited by 3 | Viewed by 1799
Abstract
Bortezomib (BTZ) is a potent proteasome inhibitor currently being used to treat multiple myeloma. However, its high toxicity and resistance to therapy severely limit the treatment outcomes. Drug–membrane interactions have a crucial role in drugs’ behavior in vivo, affecting their bioavailability and pharmacological [...] Read more.
Bortezomib (BTZ) is a potent proteasome inhibitor currently being used to treat multiple myeloma. However, its high toxicity and resistance to therapy severely limit the treatment outcomes. Drug–membrane interactions have a crucial role in drugs’ behavior in vivo, affecting their bioavailability and pharmacological activity. Additionally, drugs’ toxicity often occurs due to their effects on the cell membranes. Therefore, studying BTZ’s interactions with cell membranes may explain the limitations of its therapy. Due to the cell membranes’ complexity, lipid vesicles were proposed here as biomembrane models, focusing on the membrane’s main constituents. Two models with distinct composition and complexity were used, one composed of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and the other containing DMPC, cholesterol (Chol), and sphingomyelin (SM). BTZ’s interactions with the models were evaluated regarding the drugs’ lipophilicity, preferential location, and effects on the membrane’s physical state. The studies were conducted at different pH values (7.4 and 6.5) to mimic the normal blood circulation and the intestinal environment, respectively. BTZ revealed a high affinity for the membranes, which proved to be dependent on the drug-ionization state and the membrane complexity. Furthermore, BTZ’s interactions with the cell membranes was proven to induce changes in the membrane fluidity. This may be associated with its resistance to therapy, since the activity of efflux transmembrane proteins is dependent on the membrane’s fluidity. Full article
(This article belongs to the Special Issue Nanotechnologies and Nanoparticles Interaction with Bio-Membranes)
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13 pages, 2467 KiB  
Article
Evaluation of the Growth-Inhibitory Spectrum of Three Types of Cyanoacrylate Nanoparticles on Gram-Positive and Gram-Negative Bacteria
by Fean Davisunjaya Sarian, Kazuki Ando, Shota Tsurumi, Ryohei Miyashita, Koichi Ute and Takeshi Ohama
Membranes 2022, 12(8), 782; https://doi.org/10.3390/membranes12080782 - 15 Aug 2022
Cited by 3 | Viewed by 1487
Abstract
The development of novel effective antibacterial agents is crucial due to increasing antibiotic resistance in various bacteria. Poly (alkyl cyanoacrylate) nanoparticles (PACA-NPs) are promising novel antibacterial agents as they have shown antibacterial activity against several Gram-positive and Gram-negative bacteria. However, the antibacterial mechanism [...] Read more.
The development of novel effective antibacterial agents is crucial due to increasing antibiotic resistance in various bacteria. Poly (alkyl cyanoacrylate) nanoparticles (PACA-NPs) are promising novel antibacterial agents as they have shown antibacterial activity against several Gram-positive and Gram-negative bacteria. However, the antibacterial mechanism remains unclear. Here, we compared the antibacterial efficacy of ethyl cyanoacrylate nanoparticles (ECA-NPs), isobutyl cyanoacrylate NPs (iBCA-NPs), and ethoxyethyl cyanoacrylate NPs (EECA-NPs) using five Gram-positive and five Gram-negative bacteria. Among these resin nanoparticles, ECA-NPs showed the highest growth inhibitory effect against all the examined bacterial species, and this effect was higher against Gram-positive bacteria than Gram-negative. While iBCA-NP could inhibit the cell growth only in two Gram-positive bacteria, i.e., Bacillus subtilis and Staphylococcus aureus, it had negligible inhibitory effect against all five Gram-negative bacteria examined. Irrespective of the differences in growth inhibition induced by these three NPs, N-acetyl-L-cysteine (NAC), a well-known reactive oxygen species (ROS) scavenger, efficiently restored growth in all the bacterial strains to that similar to untreated cells. This strongly suggests that the exposure to NPs generates ROS, which mainly induces cell growth inhibition irrespective of the difference in bacterial species and cyanoacrylate NPs used. Full article
(This article belongs to the Special Issue Nanotechnologies and Nanoparticles Interaction with Bio-Membranes)
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12 pages, 2210 KiB  
Article
Intravenous Nanocarrier for Improved Efficacy of Quercetin and Curcumin against Breast Cancer Cells: Development and Comparison of Single and Dual Drug–Loaded Formulations Using Hemolysis, Cytotoxicity and Cellular Uptake Studies
by Mohammad Akhlaquer Rahman, Vineet Mittal, Shadma Wahab, Abdulrhman Alsayari, Abdullatif Bin Muhsinah and Dalia Almaghaslah
Membranes 2022, 12(7), 713; https://doi.org/10.3390/membranes12070713 - 15 Jul 2022
Cited by 10 | Viewed by 1815
Abstract
The present work highlights the suitability of an oil-based nanocarrier to deliver quercetin (Q) and curcumin (C) through the intravenous route for treatment of breast cancer. The nanoemulsion prepared by the modified emulsification-solvent evaporation method resulted in particle size (<30 nm), polydispersity index [...] Read more.
The present work highlights the suitability of an oil-based nanocarrier to deliver quercetin (Q) and curcumin (C) through the intravenous route for treatment of breast cancer. The nanoemulsion prepared by the modified emulsification-solvent evaporation method resulted in particle size (<30 nm), polydispersity index (<0.2), zeta potential (<10 mV), optimum viscosity, high encapsulation efficiency and drug loading for both drugs. The pH and osmolarity of the nanoemulsion were about 7.0 and 280 mOsm, respectively, demonstrated its suitability for intravenous administration. In-vitro release of drugs from all the formulations demonstrated initial fast release followed by sustained release for a period of 48 h. The fabricated single and dual drug–loaded nanoemulsion (QNE, CNE, QC-NE) exhibited moderate hemolysis at a concentration of 50 μg/mL. The % hemolysis caused by all the formulations was similar to their individual components (p ˃ 0.05) and demonstrated the biocompatibility of the nanoemulsion with human blood. In vitro cytotoxic potential of single and dual drug–loaded nanoemulsions were determined against breast cancer cells (MF-7). The IC50 value for QNE and CNE were found to be 40.2 ± 2.34 µM and 28.12 ± 2.07 µM, respectively. The IC50 value for QC-NE was 21.23 ± 2.16 µM and demonstrated the synergistic effect of both the drugs. The internalization of the drug inside MF-7 cells was detected by cellular uptake study. The cellular uptake of QNE and CNE was approximately 3.9-fold higher than free quercetin and curcumin (p < 0.0001). This strategically designed nanoemulsion appears to be a promising drug delivery system for the proficient primary preclinical development of quercetin and curcumin as therapeutic modalities for the treatment of breast cancer. Full article
(This article belongs to the Special Issue Nanotechnologies and Nanoparticles Interaction with Bio-Membranes)
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Review

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24 pages, 3297 KiB  
Review
Amphiphilic Gold Nanoparticles: A Biomimetic Tool to Gain Mechanistic Insights into Peptide-Lipid Interactions
by Ester Canepa, Annalisa Relini, Davide Bochicchio, Enrico Lavagna and Andrea Mescola
Membranes 2022, 12(7), 673; https://doi.org/10.3390/membranes12070673 - 29 Jun 2022
Cited by 4 | Viewed by 2527
Abstract
Functional peptides are now widely used in a myriad of biomedical and clinical contexts, from cancer therapy and tumor targeting to the treatment of bacterial and viral infections. Underlying this diverse range of applications are the non-specific interactions that can occur between peptides [...] Read more.
Functional peptides are now widely used in a myriad of biomedical and clinical contexts, from cancer therapy and tumor targeting to the treatment of bacterial and viral infections. Underlying this diverse range of applications are the non-specific interactions that can occur between peptides and cell membranes, which, in many contexts, result in spontaneous internalization of the peptide within cells by avoiding energy-driven endocytosis. For this to occur, the amphipathicity and surface structural flexibility of the peptides play a crucial role and can be regulated by the presence of specific molecular residues that give rise to precise molecular events. Nevertheless, most of the mechanistic details regulating the encounter between peptides and the membranes of bacterial or animal cells are still poorly understood, thus greatly limiting the biomimetic potential of these therapeutic molecules. In this arena, finely engineered nanomaterials—such as small amphiphilic gold nanoparticles (AuNPs) protected by a mixed thiol monolayer—can provide a powerful tool for mimicking and investigating the physicochemical processes underlying peptide-lipid interactions. Within this perspective, we present here a critical review of membrane effects induced by both amphiphilic AuNPs and well-known amphiphilic peptide families, such as cell-penetrating peptides and antimicrobial peptides. Our discussion is focused particularly on the effects provoked on widely studied model cell membranes, such as supported lipid bilayers and lipid vesicles. Remarkable similarities in the peptide or nanoparticle membrane behavior are critically analyzed. Overall, our work provides an overview of the use of amphiphilic AuNPs as a highly promising tailor-made model to decipher the molecular events behind non-specific peptide-lipid interactions and highlights the main affinities observed both theoretically and experimentally. The knowledge resulting from this biomimetic approach could pave the way for the design of synthetic peptides with tailored functionalities for next-generation biomedical applications, such as highly efficient intracellular delivery systems. Full article
(This article belongs to the Special Issue Nanotechnologies and Nanoparticles Interaction with Bio-Membranes)
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