Nanoparticle Induces Membrane Fusion in a State-wise and Property-sensitive Mode

Chi-Yun Ma; Xue-Wei Dong; Xue-Mei Lu; Bing Yuan; Kai Yang

doi:10.1007/s10118-024-3222-5

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Nanoparticle Induces Membrane Fusion in a State-wise and Property-sensitive Mode

RESEARCH ARTICLE | Updated：2024-12-31

- Nanoparticle Induces Membrane Fusion in a State-wise and Property-sensitive Mode
- Chinese Journal of Polymer Science Vol. 43, Issue 1, Pages: 235-244(2025)
- Affiliations：
  
  a.Center for Soft Condensed Matter Physics and Interdisciplinary Research & School of Physical Science and Technology, Soochow University, Suzhou 215006, China
  b.State Key Laboratory of Surface Physics and Department of Physics, Fudan University, Shanghai 200433, China
  c.School of Optical and Electronic Information, Suzhou City University, Suzhou 215104, China
  d.School of Physical Science and Technology, Jiangsu Key Laboratory of Thin Films, Soochow University, Suzhou 215006, China
  e.Songshan Lake Materials Laboratory, Dongguan 523808, China
- Author bio：
  
  dongxuewei@suda.edu.cn (X.W.D.)
  yangkai@suda.edu.cn (K.Y.)
- Funds：
- DOI：10.1007/s10118-024-3222-5
  CLC：
- Received：18 July 2024，
  
  Revised：2024-08-15，
  
  Accepted：19 August 2024，
  
  Online First：07 November 2024，
  
  Published：01 January 2025
- Accepted：
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Ma, C. Y.; Dong, X. W.; Lu, X. M.; Yuan B.; Yang, K. Nanoparticle induces membrane fusion in a state-wise and property-sensitive mode. Chinese J. Polym. Sci. 2025, 43, 235–244

Chi-Yun Ma, Xue-Wei Dong, Xue-Mei Lu, et al. Nanoparticle Induces Membrane Fusion in a State-wise and Property-sensitive Mode[J]. Chinese Journal of Polymer Science, 2025, 43(1): 235-244.
Ma, C. Y.; Dong, X. W.; Lu, X. M.; Yuan B.; Yang, K. Nanoparticle induces membrane fusion in a state-wise and property-sensitive mode. Chinese J. Polym. Sci. 2025, 43, 235–244 DOI： 10.1007/s10118-024-3222-5.

Chi-Yun Ma, Xue-Wei Dong, Xue-Mei Lu, et al. Nanoparticle Induces Membrane Fusion in a State-wise and Property-sensitive Mode[J]. Chinese Journal of Polymer Science, 2025, 43(1): 235-244. DOI： 10.1007/s10118-024-3222-5.

摘要

NP-induced membrane fusion behaviors are systematically investigated by performing extensive CG-MD simulations. The vesicle-bilayer fusion induced by a hydrophobic NP is an intricately state-wise process. Moreover

NP properties (size

hydrophobicity and hydrophilicity) have distinct effects on membrane fusion and thus the optimal NP conditions for facilitating membrane fusion are obtained.

Abstract

Membrane fusion is essential for many cellular physiological functions

which is modulated by highly precise molecular mechanism involving multiple energy barriers. Nanoparticles (NPs)

which exhibit immense potential in the field of biomedical applications

can act as fusogen proteins to initiate and regulate membrane fusion. However

the underlying mechanisms of NP-induced membrane fusion and the molecular details involved remain largely elusive. Here

using coarse-grained molecular dynamics simulations

we systematically investigate the NP-induced membrane fusion behaviors and the influences of NP properties (size

hydrophobicity and hydrophilicity). Our results show that the vesicle-bilayer fusion induced by a hydrophobic NP is an intricately state-wise process

involving the approach and local deformation of the vesicle and bilayer bridging by the NP

the flip-flop of lipids from proximal leaflets and the formation of a fusion stalk

as well as further lipid interactions between distal leaflets and complete fusion. Moreover

we find that NP properties have distinct effects on membrane fusion and thus the optimal NP conditions for facilitating membrane fusion are obtained. Our work provides a mechanistic understanding of NP-induced membrane fusion and offers useful insights for efficient and controlled regulation of membrane fusion.

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references

Martens, S.; McMahon, H. T. Mechanisms of membrane fusion: disparate players and common principles. Nat. Rev. Mol. Cell Biol. 2008 , 9 , 543−556..

Bonifacino, J. S.; Glick, B. S. The mechanisms of vesicle budding and fusion. Cell 2004 , 116 , 153−166..

Wang, Y.; Li, L.; Hou, C.; Lai, Y.; Long, J.; Liu, J.; Zhong, Q.; Diao, J. SNARE-mediated membrane fusion in autophagy. Semin. Cell Dev. Biol. 2016 , 60 , 97−104..

Yang, Z.; Gou, L.; Chen, S.; Li, N.; Zhang, S.; Zhang, L. Membrane fusion involved in neurotransmission: glimpse from electron microscope and molecular simulation. Front. Mol. Neurosci. 2017 , 10 , 168..

Han, J.; Pluhackova, K.; Böckmann, R. A. The multifaceted role of SNARE proteins in membrane fusion. Front. Physiol. 2017 , 8 , 5..

Brunger, A. T.; Choi, U. B.; Lai, Y.; Leitz, J.; Zhou, Q. Molecular mechanisms of fast neurotransmitter release. Annu. Rev. Biophys. 2018 , 47 , 469−497..

Tolar, L. A.; Pallanck, L. NSF function in neurotransmitter release involves rearrangement of the SNARE complex downstream of synaptic vesicle docking. J. Neurosci. 1998 , 18 , 10250−10256..

Mahapatra, S.; Takahashi, T. Physiological roles of endocytosis and presynaptic scaffold in vesicle replenishment at fast and slow central synapses. eLife 2024 , 12 , RP90497..

Jiang, E.; Yan, T.; Xu, Z.; Shang, Z. Tumor microenvironment and cell fusion. Biomed Res. Int. 2019 , 2019 , 5013592..

Mazur, F.; Chandrawati, R. Membrane fusion models for bioapplications. ChemNanoMat 2021 , 7 , 223−237..

Arribas Perez, M.; Beales, P. A. Biomimetic curvature and tension-driven membrane fusion induced by silica nanoparticles. Langmuir 2021 , 37 , 13917−13931..

Jahn, R.; Lang, T.; Südhof, T. C. Membrane fusion. Cell 2003 , 112 , 519−533..

Chernomordik, L. V.; Kozlov, M. M. Mechanics of membrane fusion. Nat. Struct. Mol. Biol. 2008 , 15 , 675−683..

Marrink, S. J.; Mark, A. E. The mechanism of vesicle fusion as revealed by molecular dynamics simulations. J. Am. Chem. Soc. 2003 , 125 , 11144−11145..

Kawamoto, S.; Shinoda, W. Free energy analysis along the stalk mechanism of membrane fusion. Soft matter 2014 , 10 , 3048−3054..

Schneck, E.; Sedlmeier, F.; Netz, R. R. Hydration repulsion between biomembranes results from an interplay of dehydration and depolarization. Proc. Natl. Acad. Sci. U.S.A. 2012 , 109 , 14405−14409..

Kawamoto, S.; Klein, M. L.; Shinoda, W. Coarse-grained molecular dynamics study of membrane fusion: Curvature effects on free energy barriers along the stalk mechanism. J. Chem. Phys. 2015 , 143 , 243112 ..

Li, F.; Tiwari, N.; Rothman, J. E.; Pincet, F. Kinetic barriers to SNAREpin assembly in the regulation of membrane docking/priming and fusion. Proc. Natl. Acad. Sci. U. S. A. 2016 , 113 , 10536−10541..

D'Agostino, M.; Risselada, H. J.; Endter, L. J.; Comte-Miserez, V.; Mayer, A. SNARE-mediated membrane fusion arrests at pore expansion to regulate the volume of an organelle. EMBO J. 2018 , 37 , e99193..

Risselada, H. J.; Kutzner, C.; Grubmüller, H. Caught in the act: visualization of SNARE-mediated fusion events in molecular detail. ChemBioChem 2011 , 12 , 1049−1055..

Vrljic, M.; Strop, P.; Ernst, J. A.; Sutton, R. B.; Chu, S.; Brunger, A. T. Molecular mechanism of the synaptotagmin-SNARE interaction in Ca2+-triggered vesicle fusion. Nat. Struct. Mol. Biol. 2010 , 17 , 325−331..

Sun, Y.; Tien, P. From endocytosis to membrane fusion:emerging roles of dynamin in virus entry. Crit. Rev. Microbiol. 2013 , 39 , 166−179..

Akimov, S. A.; Polynkin, M. A.; Jiménez-Munguía, I.; Pavlov, K. V.; Batishchev, O. V. Phosphatidylcholine membrane fusion is pH-dependent. Int. J. Mol. Sci. 2018 , 19 , 1358..

Allolio, C.; Harries, D. Calcium ions promote membrane fusion by forming negative-curvature inducing clusters on specific anionic lipids. ACS nano 2021 , 15 , 12880−12887..

Mondal Roy, S.; Sarkar, M. Membrane fusion induced by small molecules and ions. J. Lipids 2011 , 2011 , 528784..

Dimova, R.; Riske, K. A.; Aranda, S.; Bezlyepkina, N.; Knorr, R. L.; Lipowsky, R. Giant vesicles in electric fields. Soft matter 2007 , 3 , 817−827..

Malinin, V. S.; Lentz, B. R. Energetics of vesicle fusion intermediates: comparison of calculations with observedeffects of osmotic and curvature stresses. Biophys. J. 2004 , 86 , 2951−2964..

François-Martin, C.; Bacle, A.; Rothman, J. E.; Fuchs, P. F.; Pincet, F. Cooperat ion of conical and polyunsaturated lipids to regulate initiation and processing of membrane fusion. Front. Mol. Biosci. 2021 , 8 , 763115..

Kasson, P. M.; Pande, V. S. Control of membrane fusion mechanism by lipid composition: predictions from ensemble molecular dynamics. PLoS Comput. Biol. 2007 , 3 , e220..

Shillcock, J. C.; Lipowsky, R. Tension-induced fusion of bilayer membranes and vesicles. Nat. Mater. 2005 , 4 , 225−228..

Gao, L.; Lipowsky, R.; Shillcock, J. Tension-induced vesicle fusion: pathways and pore dynamics. Soft Matter 2008 , 4 , 1208−1214..

Mora, N. L.; Bahreman, A.; Valkenier, H.; Li, H.; Sharp, T. H.; Sheppard, D. N.; Davis, A. P.; Kros, A. Targeted anion transporter delivery by coiled-coil driven membrane fusion. Chem. Sci. 2016 , 7 , 1768−1772..

Versluis, F.; Voskuhl, J.; van Kolck, B.; Zope, H.; Bremmer, M.; Albregtse, T.; Kros, A. In situ modification of plain liposomes with lipidated coiled coil forming peptides induces membrane fusion. J. Am. Chem. Soc. 2013 , 135 , 8057−8062..

Kong, L.; Askes, S. H.; Bonnet, S.; Kros, A.; Campbell, F. Temporal control of membrane fusion through photolabile PEGylation of liposome membranes. Angew. Chem. Int. Ed. 2016 , 55 , 1396−1400..

Zope, H. R.; Versluis, F.; Ordas, A.; Voskuhl, J.; Spaink, H. P.; Kros, A. In vitro and in vivo supramolecular modification of biomembranes using a lipidated coiled-coil motif. Angew. Chem. Int. Ed. 2013 , 52 , 14247−14251..

Stengel, G.; Zahn, R.; Höök, F. DNA-induced programmable fusion of phospholipid vesicles. J. Am. Chem. Soc. 2007 , 129 , 9584−9585..

Malle, M. G.; Löffler, P. M.; Bohr, S. S.-R.; Sletfjerding, M. B.; Risgaard, N. A.; Jensen, S. B.; Zhang, M.; Hedegård, P.; Vogel, S.; Hatzakis, N. S. Single-particle combinatorial multiplexed liposome fusion mediated by DNA. Nat. Chem. 2022 , 14 , 558−565..

Paez-Perez, M.; Russell, I. A.; Cicuta, P.; Di Michele, L. Modulating membrane fusion through the design of fusogenic DNA circuits and bilayer composition. Soft Matter 2022 , 18 , 7035−7044..

Blasco, S.; Sukeník, L.; Vácha, R. Nanoparticle induced fusion of lipid membranes. Nanoscale 2024 , 16 , 10221−10229..

Bhaskara, R. M.; Linker, S. M.; Vögele, M.; Köfinger, J.; Hummer, G. Carbon nanotubes mediate fusion of lipid vesicles. ACS nano 2017 , 11 , 1273−1280..

Ho, N. T.; Siggel, M.; Camacho, K. V.; Bhaskara, R. M.; Hicks, J. M.; Yao, Y.-C.; Zhang, Y.; Köfinger, J.; Hummer, G.; Noy, A. Membrane fusion and drug delivery with carbon nanotube porins. Proc. Natl. Acad. Sci. U.S.A. 2021 , 118 , e2016974118..

Tahir, M. A.; Guven, Z. P.; Arriaga, L. R.; Tinao, B.; Yang, Y.-S. S.; Bekdemir, A.; Martin, J. T.; Bhanji, A. N.; Irvine, D.; Stellacci, F.; Alexander-Katz, A. Calcium-triggered fusion of lipid membranes is enabled by amphiphilic nanoparticles. Proc. Natl. Acad. Sci. U.S.A. 2020 , 117 , 18470−18476..

Canepa, E.; Bochicchio, D.; Brosio, G.; Silva, P. H. J.; Stellacci, F.; Dante, S.; Rossi, G.; Relini, A. Cholesterol-containing liposom es decorated with Au nanoparticles as minimal tunable fusion machinery. Small 2023 , 19 , 2207125..

Rørvig-Lund, A.; Bahadori, A.; Semsey, S.; Bendix, P. M.; Oddershede, L. B. Vesicle fusion triggered by optically heated gold nanoparticles. Nano Lett. 2015 , 15 , 4183−4188..

Berry, C. C.; Curtis, A. S. Functionalisation of magnetic nanoparticles for applications in biomedicine. J. Phys. D: Appl. Phys. 2003 , 36 , R198−R206..

Tao, Y.; Li, M.; Kim, B.; Auguste, D. T. Incorporating gold nanoclusters and target-directed liposomes as a synergistic amplified colorimetric sensor for HER2-positive breast cancer cell detection. Theranostics 2017 , 7 , 899−911..

Mayer, K. M.; Hao, F.; Lee, S.; Nordlander, P.; Hafner, J. H. A single molecule immunoassay by localized surface plasmon resonance. Nanotechnology 2010 , 21 , 255503..

Wolfbeis, O. S. An overview of nanoparticles commonly used in fluorescent bioimaging. Chem. Soc. Rev. 2015 , 44 , 4743−476 8..

Gao, X.; Cui, Y.; Levenson, R. M.; Chung, L. W.; Nie, S. In vivo cancer targeting and imaging with semiconductor quantum dots. Nat. Biotechnol. 2004 , 22 , 969−976..

Cheng, Q.; Wei, T.; Farbiak, L.; Johnson, L. T.; Dilliard, S. A.; Siegwart, D. J. Selective organ targeting (SORT) nanoparticles for tissue-specific mRNA delivery and CRISPR–Cas gene editing. Nat. Nanotechnol. 2020 , 15 , 313−320..

Johnstone, T. C.; Suntharalingam, K.; Lippard, S. J. The next generation of platinum drugs: targeted Pt (II) agents, nanoparticle delivery, and Pt (IV) prodrugs. Chem. Rev. 2016 , 116 , 3436−3486..

Sun, T.; Zhang, Y. S.; Pang, B.; Hyun, D. C.; Yang, M.; Xia, Y. in Nanomaterials and Neoplasms , Jenny Stanford Publishing New Delhi, India, 2021 , p. 31−142..

Lung, P.; Yang, J.; Li, Q. Nanoparticle formulated vaccines: opportunities and challenges. Nanoscale 2020 , 12 , 5746−5763..

Lewin, M.; Carlesso, N.; Tung, C.-H.; Tang, X.-W.; Cory, D.; Scadden, D. T.; Weissleder, R. Tat peptide-derivatized magnetic nanoparticles allow in vivo tracking and recovery of progenitor cells. Nat. Biotechnol. 2000 , 18 , 410−414..

Jin, D.; Xi, P.; Wang, B.; Zhang, L.; Enderlein, J.; van Oijen, A. M. Nanoparticles for super-resolution microscopy and single-molecule tracking. Nat. Methods 2018 , 15 , 415−423..

He, K.; Wei, Y.; Zhang, Z.; Chen, H.; Yuan, B.; Pang, H.-B.; Yang, K. Membrane-curvature-mediated co-endocytosis of bystander and functional nanoparticles. Nanoscale 2021 , 13 , 9626−9633..

Yang, K.; Ma, Y.-Q. Computer simulation of the translocation of nanoparticles with different shapes across a lipid bilayer. Nat. Nanotechnol. 2010 , 5 , 579−583..

Chen, H.; Dong, X.; Ou, L.; Ma, C.; Yuan, B.; Yang, K. Thermal-controlled cellular uptake of “hot” nanoparticles. Nanoscale 2023 , 15 , 12718−12727..

Li, Y.; Zhang, M.; Niu, X.; Yue, T. Selective membrane wrapping on differently sized nanoparticles regulated by clathrin assembly: A computational model. Colloids Surf. B: Biointerfaces 2022 , 214 , 112467..

Ou, L.; Chen, H.; Yuan, B.; Yang, K. Membrane-specific binding of 4 nm lipid nanoparticles mediated by an entropy-driven interaction mechanism. ACS Nano 2022 , 16 , 18090−18100..

Shen, Z.; Ye, H.; Yi, X.; Li, Y. Membrane wrapping efficiency of elastic nanoparticles during endocytosis: size and shape matter. ACS nano 2018 , 13 , 215−228..

Yan, Z.; Wu, Z.; Li, S.; Zhang, X.; Yi, X.; Yue, T. Curvature-mediated cooperative wrapping of multiple nanoparticles at the same and opposite membrane sides. Nanoscale 2019 , 11 , 19751−19762..

Huang, C.; Zhang, Y.; Yuan, H.; Gao, H.; Zhang, S. Role of nanoparticle geometry in endocytosis: laying down to stand up. Nano Lett. 2013 , 13 , 4546−4550..

Wan, H. X.; Xu, D.; Dong, X. W.; Yang, K.; Yan, L. T. Insight into biophysicochemical principles of biopolymers through simulation and theory. Chinese J. Polym. Sci. 2023 , 41 , 1342−1354..

Li, W.; Ma, Y.; Ou, L.; Xu, C.; Wei, Y.; Yang, K.; Yuan, B. Asymmetric disturbance and permeabilization of bilayer membranes by 3-nm carbon dots. J. Hazard. Mater. 2024 , 465 , 133382..

Wei, L.; Tu, W.; Xu, Y.; Xu, C.; Dou, Y.; Ge, Y.; Sun, S.; Wei, Y.; Yang, K.; Yuan, B. Assembly-Induced Membrane Selectivity of Artificial Model Peptides through Entropy–Enthalpy Competition. ACS Nano 2024 , 18 , 18650−18662..

Wu, J.; Xu, C.; Ye, Z.; Chen, H.; Wang, Y.; Yang, K.; Yuan, B. Transition between Different Diffusion Modes of Individual Lipids during the Membrane-Specific Action of As-CATH4 Peptides. Small 2023 , 19 , e2301713..

Pronk, S.; Páll, S.; Schulz, R.; Larsson, P.; Bjelkmar, P.; Apostolov, R.; Shirts, M. R.; Smith, J. C.; Kasson, P. M.; Van Der Spoel, D.; Hess, B.; Lindahl, E. GROMACS 4.5: a high-throughput and highly parallel open source molecular simulation toolkit. Bioinformatics 2013 , 29 , 845−854..

Van Der Spoel, D.; Lindahl, E.; Hess, B.; Groenhof, G.; Mark, A. E.; Berendsen, H. J. GROMACS: fast, flexible, and free. J. Comput. Chem. 2005 , 26 , 1701−1718..

Berendsen, H. J.; van der Spoel, D.; van Drunen, R. GROMACS: A message-passing parallel molecular dynamics implementation. Comput. Phys. Commun. 1995 , 91 , 43−56..

Hess, B.; Kutzner, C.; van Der Spoel, D.; Lindahl, E. GROMACS 4: algorithms for highly efficient, load-balanced, and scalable molecular simulation. J. Chem. Theory Comput. 2008 , 4 , 435−447..

Marrink, S. J.; Tieleman, D. P. Perspective on the Martini model. Chem. Soc. Rev. 2013 , 42 , 6801−6822..

Marrink, S. J.; Risselada, H. J.; Yefimov, S.; Tieleman, D. P.; De Vries, A. H. The MARTINI force field: coarse grained model for biomolecular simulations. J. Phys. Chem. B 2007 , 111 , 7812−7824..

Alessandri, R.; Grünewald, F.; Marrink, S. J. The martini model in materials science. Adv. Mater. 2021 , 33 , e2008635..

Marrink, S. J.; Monticelli, L.; Melo, M. N.; Alessandri, R.; Tieleman, D. P.; Souza, P. C. Two decades of Martini: Better beads, broader scope. WIREs. Comput. Mol. Sci. 2023 , 13 , e1620..

Barnoud, J.; Monticelli, L. in Molecular Modeling of Proteins , Humana Press, New York, 2015 , p. 125−149..

Claveras Cabezudo, A.; Athanasiou, C.; Tsengenes, A.; Wade, R. C. Scaling protein–water interactions in the martini 3 coarse-grained force field to simulate transmembrane helix dimers in different lipid environments. J. Chem. Theory Comput. 2023 , 19 , 2109−2119..

Badhe, Y.; Kumar, D.; Gupta, R.; Jain, V.; Rai, B. Coarse grained MD simulation of bulk and interfacial behavior of mixture of CTAB/SDS surfactants. J. Mol. Model. 2024 , 30 , 162..

Jo, S.; Kim, T.; Iyer, V. G.; Im, W. CHARMM-GUI: a web-based graphical user interface for CHARMM. J. Comput. Chem. 2008 , 29 , 1859−1865..

Qi, Y.; Ingólfsson, H. I.; Cheng, X.; Lee, J.; Marrink, S. J.; Im, W. CHARMM-GUI martini maker for coarse-grained simulations with the martini force field. J. Chem. Theory Comput. 2015 , 11 , 4486−4494..

Hsu, P. C.; Bruininks, B. M.; Jefferies, D.; Cesar Telles de Souza, P.; Lee, J.; Patel, D. S.; Marrink, S. J.; Qi, Y.; Khalid, S.; Im, W. CHARMM-GUI Martini Maker for modeling and simulation of complex bacterial membranes with lipopolysaccharides. J. Comput. Chem. 2017 , 38 , 2354−2363..

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