{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T03:11:42Z","timestamp":1760238702314,"version":"build-2065373602"},"reference-count":42,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2022,8,15]],"date-time":"2022-08-15T00:00:00Z","timestamp":1660521600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Vesicles formed by DMPC liposomes externally conjugated with branched polyglycerol-dendrons as well as linear PEG in water solution were simulated using the DPD method. Such a structure of vesicles corresponds to the structure of polymer-grafted liposomes obtained experimentally by the post-insertion method, in which polymer chains are fixed on the outer surface of the liposome. The grafting density, generation number and spacer length of grafted dendrons were varied. It was shown that modification of the outer surface of liposomes due to grafting of hydrophilic dendrons has practically no effect on the size and shape of the vesicle, as well as on the morphology of the lipid membrane up to certain critical thresholds of grafting density, degree of polymerization, and generation number of grafted molecules. Exceeding the threshold values of these structural parameters leads to irreversible deformation of the lipid membrane. Diffusion through the membrane and the transition of grafted molecules from the outer surface of the liposome to the inner surface is not observed for dendrons with a generation number higher than one, even at high grafting densities. The critical values of the generation number and the characteristics of the molecular coating at these values were determined for various grafting densities and spacer lengths of the grafted chains. It was shown that the chemical potential of the grafted dendron can serve as a stability metric for the conjugated liposome. The chemical potential of grafted molecules was calculated using the mean field model of the spherical brush on the liposome surface. An analysis of the simulation data shows that, within the framework of the applicability of the mean field approach, the value of the chemical potential is a sufficient criterion for separating vesicles into stable and unstable forms. These results can be used as a guide for the experimental design of nanocontainers based on lipid vesicles with an external protective coating of branched macromolecules.<\/jats:p>","DOI":"10.3390\/ijms23169142","type":"journal-article","created":{"date-parts":[[2022,8,15]],"date-time":"2022-08-15T20:58:08Z","timestamp":1660597088000},"page":"9142","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Stability of DMPC Liposomes Externally Conjugated with Branched Polyglycerol"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0422-3856","authenticated-orcid":false,"given":"Alexander A.","family":"Beketov","sequence":"first","affiliation":[{"name":"Center for Chemical Engineering, St. Petersburg National Research University of Information Technologies, Mechanics and Optics, 197101 St. Petersburg, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5591-1002","authenticated-orcid":false,"given":"Ivan V.","family":"Mikhailov","sequence":"additional","affiliation":[{"name":"Institute of Macromolecular Compounds, Russian Academy of Sciences, 199004 St. Petersburg, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6715-1389","authenticated-orcid":false,"given":"Anatoly A.","family":"Darinskii","sequence":"additional","affiliation":[{"name":"Institute of Macromolecular Compounds, Russian Academy of Sciences, 199004 St. Petersburg, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1016\/S0006-291X(75)80433-5","article-title":"The Effect of Particle Size and Charge on the Clearance Rates of Liposomes and Liposome Encapsulated Drugs","volume":"63","author":"Juliano","year":"1975","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.addr.2012.09.037","article-title":"Liposomal Drug Delivery Systems: From Concept to Clinical Applications","volume":"65","author":"Allen","year":"2013","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/0005-2736(91)90201-I","article-title":"Pharmacokinetics of Stealth versus Conventional Liposomes: Effect of Dose","volume":"1068","author":"Allen","year":"1991","journal-title":"Biochim. Biophys. Acta Biomembr."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2601","DOI":"10.1021\/cr00040a001","article-title":"The \u201cStealth\u201d Liposome: A Prototypical Biomaterial","volume":"95","author":"Lasic","year":"1995","journal-title":"Chem. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1405","DOI":"10.1007\/s11095-007-9284-6","article-title":"Poly(ethylene Glycol)-Modified Nanocarriers for Tumor-Targeted and Intracellular Delivery","volume":"24","author":"Vyas","year":"2007","journal-title":"Pharm. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1021\/ar900158p","article-title":"Hyperbranched Polyglycerols: From the Controlled Synthesis of Biocompatible Polyether Polyols to Multipurpose Applications","volume":"43","author":"Wilms","year":"2010","journal-title":"Acc. Chem. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1021\/bm901123j","article-title":"Hyperbranched Polyglycerol-Based Lipids via Oxyanionic Polymerization: Toward Multifunctional Stealth Liposomes","volume":"11","author":"Hofmann","year":"2010","journal-title":"Biomacromolecules"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3078","DOI":"10.1021\/acs.macromol.7b00413","article-title":"Synthesis of Well-Defined Phthalimide Monofunctional Hyperbranched Polyglycerols and Its Transformation to Various Conjugation Relevant Functionalities","volume":"50","author":"Kasza","year":"2017","journal-title":"Macromolecules"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2506","DOI":"10.1021\/acs.biomac.8b00115","article-title":"Comparison of Linear and Hyperbranched Polyether Lipids for Liposome Shielding by 18F-Radiolabeling and Positron Emission Tomography","volume":"19","author":"Wagener","year":"2018","journal-title":"Biomacromolecules"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2831","DOI":"10.1002\/chem.200306073","article-title":"Self-Assembled Monolayers of Dendritic Polyglycerol Derivatives on Gold That Resist the Adsorption of Proteins","volume":"10","author":"Siegers","year":"2004","journal-title":"Chem. A Eur. J."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"4907","DOI":"10.1021\/la702867t","article-title":"Self-Assembled Monothiol-Terminated Hyperbranched Polyglycerols on a Gold Surface: A Comparative Study on the Structure, Morphology, and Protein Adsorption Characteristics with Linear Poly(ethylene Glycol)s","volume":"24","author":"Yeh","year":"2008","journal-title":"Langmuir"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1039\/C8MD00515J","article-title":"Diversity of PEGylation methods of liposomes and their influence on RNA delivery","volume":"10","author":"Nosova","year":"2019","journal-title":"Med. Chem. Commun."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"542","DOI":"10.3390\/pharmaceutics5040542","article-title":"Surface Engineering of Liposomes for Stealth Behavior","volume":"5","author":"Nag","year":"2013","journal-title":"Pharmaceutics"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1021\/bc990135y","article-title":"Poly(ethylene glycol)-modification of the phospholipid vesicles by using the spontaneous incorporation of poly(ethylene glycol)-lipid into the vesicles","volume":"11","author":"Sou","year":"2000","journal-title":"Bioconjug Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2801","DOI":"10.1016\/j.bbamem.2012.06.019","article-title":"Comparative studies of polyethylene glycol-modified liposomes prepared using different PEG-modification methods","volume":"1818","author":"Nakamura","year":"2012","journal-title":"Biophys. Acta."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/0014-5793(96)00452-8","article-title":"Insertion of poly(ethylene glycol) derivatized phospholipid into pre-formed liposomes results in prolonged in vivo circulation time","volume":"386","author":"Uster","year":"1996","journal-title":"FEBS Lett."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3999","DOI":"10.1021\/acs.langmuir.8b03829","article-title":"Shape and Phase Transitions in a PEGylated Phospholipid System","volume":"35","author":"Viitala","year":"2019","journal-title":"Langmuir"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1039\/C8ME00029H","article-title":"A multiscale approach to study molecular and interfacial characteristics of vesicles","volume":"3","author":"Yu","year":"2018","journal-title":"Mol. Syst. Des. Eng."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1039\/D0NA00773K","article-title":"Dendronized vesicles: Formation, self-organization of dendron-grafted amphiphiles and stability","volume":"3","author":"Banerjee","year":"2021","journal-title":"Nanoscale Adv."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2465","DOI":"10.1103\/PhysRevLett.83.2465","article-title":"Coiling of Cylindrical Membrane Stacks with Anchored Polymers","volume":"83","author":"Frette","year":"1999","journal-title":"Phys. Rev. Lett."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1138","DOI":"10.1103\/PhysRevLett.86.1138","article-title":"Pearling instabilities of membrane tubes with anchored polymers","volume":"86","author":"Tsafrir","year":"2001","journal-title":"Phys. Rev. Lett."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"138102","DOI":"10.1103\/PhysRevLett.91.138102","article-title":"Budding and Tubulation in Highly Oblate Vesicles by Anchored Amphiphilic Molecules","volume":"91","author":"Tsafrir","year":"2003","journal-title":"Phys. Rev. Lett."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"9739","DOI":"10.1063\/1.478939","article-title":"On the role of hydrodynamic interactions in block copolymer microphase separation","volume":"110","author":"Groot","year":"1999","journal-title":"J. Chem. Phys."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1734","DOI":"10.1103\/PhysRevE.52.1734","article-title":"Hydrodynamics from dissipative particle dynamics","volume":"52","author":"Espanol","year":"1995","journal-title":"Phys. Rev. E."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1209\/0295-5075\/19\/3\/001","article-title":"Simulating microscopic hydrodynamic phenomena with dissipative particle dynamics","volume":"19","author":"Hoogerbrugge","year":"1992","journal-title":"EPL Europhys. Lett."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"8713","DOI":"10.1063\/1.476300","article-title":"Dynamic simulation of diblock copolymer microphase separation","volume":"108","author":"Groot","year":"1998","journal-title":"J. Chem. Phys."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1016\/S0006-3495(01)75737-2","article-title":"Mesoscopic simulation of cell membrane damage, morphology change and rupture by nonionic surfactants","volume":"81","author":"Groot","year":"2001","journal-title":"Biophys. J."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2658","DOI":"10.1016\/j.bpj.2008.11.073","article-title":"The Fusion of Membranes and Vesicles: Pathway and Energy Barriers from Dissipative Particle Dynamics","volume":"96","author":"Shillcock","year":"2009","journal-title":"Biophys. J."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1007\/s11426-008-0077-5","article-title":"Dissipative particle dynamics simulation study of the bilayer-vesicle transition","volume":"51","author":"Wu","year":"2008","journal-title":"China Ser. B Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3545","DOI":"10.1529\/biophysj.104.048876","article-title":"Particle Size Distribution in DMPC Vesicles Solutions Undergoing Different Sonication Times","volume":"88","author":"Maulucci","year":"2005","journal-title":"Biophys J."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"13294","DOI":"10.1039\/C7CP01530E","article-title":"Self-assembled core\u2013polyethylene glycol\u2013lipid shell nanoparticles demonstrate high stability in shear flow","volume":"19","author":"Shen","year":"2017","journal-title":"Phys. Chem. Chem. Phys."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"7703","DOI":"10.1021\/acs.nanolett.9b02646","article-title":"Spherical nanovesicles transform into a multitude of nonspherical shapes","volume":"19","author":"Ghosh","year":"2019","journal-title":"Nano Lett."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"4878","DOI":"10.1021\/ma900479y","article-title":"Properties of Dendrimers with Flexible Spacer-Chains: A Monte Carlo Study","volume":"42","author":"Klos","year":"2009","journal-title":"Macromolecules"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/0032-3950(89)90371-7","article-title":"Structure and Conformational Transitions in Grafted Polymer Chains Layers: New Theory","volume":"31","author":"Zhulina","year":"1989","journal-title":"Polym. Sci. USSR"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"8784","DOI":"10.1021\/ma010917y","article-title":"Classical Path Analysis of end-Grafted Dendrimers: Dendrimer Forest","volume":"34","author":"Pickett","year":"2001","journal-title":"Macromolecules"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1209\/0295-5075\/30\/4\/001","article-title":"Statistical Mechanics of Dissipative Particle Dynamics","volume":"30","author":"Espanol","year":"1995","journal-title":"EPL Europhys. Lett."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"4423","DOI":"10.1063\/1.474784","article-title":"Dissipative Particle Dynamics: Bridging the Gap Between Atomistic and Mesoscopic Simulation","volume":"107","author":"Groot","year":"1997","journal-title":"J. Chem. Phys."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"218101","DOI":"10.1103\/PhysRevLett.98.218101","article-title":"Pathway of membrane fusion with two tension-dependent energy barriers","volume":"98","author":"Shillcock","year":"2007","journal-title":"Phys. Rev. Lett."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2626","DOI":"10.1529\/biophysj.104.056606","article-title":"Structure of fully hydrated fluid phase dmpc and dlpc lipid bilayers using x-ray scattering from oriented multilamellar arrays and from unilamellar vesicles","volume":"88","author":"Kucerka","year":"2005","journal-title":"Biophys. J."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2702","DOI":"10.1016\/S0006-3495(02)75279-X","article-title":"Lateral diffusion of cholesterol and dimyristoylphosphatidylcholine in a lipid bilayer measured by pulsed field gradient NMR spectroscopy","volume":"83","author":"Lindblom","year":"2002","journal-title":"Biophys. J."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/S0304-4157(00)00016-2","article-title":"Structure of lipid bilayers","volume":"1469","author":"Nagle","year":"2000","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"13186","DOI":"10.1021\/jp9058966","article-title":"A coarse-grained model for polyethylene oxide and polyethylene glycol: Conformation and hydrodynamics","volume":"113","author":"Lee","year":"2009","journal-title":"J. Phys. Chem. B"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/16\/9142\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:08:53Z","timestamp":1760141333000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/16\/9142"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,15]]},"references-count":42,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2022,8]]}},"alternative-id":["ijms23169142"],"URL":"https:\/\/doi.org\/10.3390\/ijms23169142","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2022,8,15]]}}}