{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:19:47Z","timestamp":1760059187202,"version":"build-2065373602"},"reference-count":33,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,5,28]],"date-time":"2025-05-28T00:00:00Z","timestamp":1748390400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of Health","award":["AI133634","AI163708","CBET-2226779"],"award-info":[{"award-number":["AI133634","AI163708","CBET-2226779"]}]},{"name":"UMass Amherst","award":["AI133634","AI163708","CBET-2226779"],"award-info":[{"award-number":["AI133634","AI163708","CBET-2226779"]}]},{"DOI":"10.13039\/100000001","name":"NSF","doi-asserted-by":"publisher","award":["AI133634","AI163708","CBET-2226779"],"award-info":[{"award-number":["AI133634","AI163708","CBET-2226779"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Zaire Ebolavirus (EBOV) is one type of filovirus that causes the deadly EBOV disease, with an average fatality rate of around 50%. EBOV outbreaks are devastating and unpredictable and may emerge as the next global pandemic. As a BSL-4 pathogen, EBOV is inaccessible to regular biological laboratories. Therefore, EBOV virus-like particles (EBOV-VLPs) and EBOV pseudoviruses (EBOV-PVs) are utilized in the initial development of many potential therapies, for safety reasons and ease of procurement, as opposed to using infectious viruses. To investigate the host cell entry of EBOV and develop viral entry blockers, the EBOV model virions must accurately represent the morphological and mechanical properties of infectious EBOV virions. Due to the nanometer scale and irregular shape of EBOVs, these properties are challenging to characterize. In this research, state-of-the-art nanoscale characterization techniques are employed to examine the mechanical and structural elements of a selection of commonly used EBOV-approximating model virions. This study comprehensively determines the accuracy of EBOV approximation with a variety of model virions and the uniformity of mechanical and structural traits across different model virion types and preparation methods. This provides important implications for developing therapeutic treatments against EBOV using these model virions.<\/jats:p>","DOI":"10.3390\/ijms26115185","type":"journal-article","created":{"date-parts":[[2025,5,28]],"date-time":"2025-05-28T08:12:47Z","timestamp":1748419967000},"page":"5185","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Nanoscale Mechanical and Morphological Characterization of Ebolavirus-like Particles: Implications for Therapeutic Development"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-4083-5689","authenticated-orcid":false,"given":"Hannah","family":"Hargrove","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering and Department of Chemical Engineering, University of Massachusetts Amherst, Amherst, MA 01003, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susana A.","family":"Torres-Hurtado","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering and Department of Chemical Engineering, University of Massachusetts Amherst, Amherst, MA 01003, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9892-4484","authenticated-orcid":false,"given":"Wendy J.","family":"Maury","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Iowa, Iowa City, IA 52242, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8778-595X","authenticated-orcid":false,"given":"Xiaohui Frank","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering and Department of Chemical Engineering, University of Massachusetts Amherst, Amherst, MA 01003, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,28]]},"reference":[{"key":"ref_1","unstructured":"Stahelin, R.V. (2014). Membrane binding and bending in Ebola VP40 assembly and egress. Front. Microbiol., 18."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Jain, S., Martynova, E., Rizvanov, A., Khaiboullina, S., and Baranwal, M. (2021). Structural and Functional Aspects of Ebola Virus Proteins. Pathogens, 10.","DOI":"10.3390\/pathogens10101330"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1016\/S0140-6736(10)60667-8","article-title":"Ebola haemorrhagic fever","volume":"377","author":"Feldmann","year":"2011","journal-title":"Lancet"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"4275","DOI":"10.1073\/pnas.1120453109","article-title":"Structural dissection of Ebola virus and its assembly determinants using cryo-electron tomography","volume":"109","author":"Bharat","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Wu, Z., Wang, C., Li, Z., Zhang, Y., Zhang, X.E., and Cui, Z. (2019). Ebola Virus Uptake into Polarized Cells from the Apical Surface. MDPI Viruses, 11.","DOI":"10.3390\/v11121117"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2189","DOI":"10.4103\/jfmpc.jfmpc_297_19","article-title":"Ebola virus: A global public health menace: A narrative review","volume":"8","author":"Hasan","year":"2019","journal-title":"J. Family Med. Prim. Care"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"6597","DOI":"10.1016\/j.vaccine.2016.06.071","article-title":"Live Virus Vaccines Based on a Vesicular Stomatitis Virus (VSV) Backbone: Standardized Template with Key Considerations for a Risk\/Benefit Assessment","volume":"34","author":"Clarke","year":"2016","journal-title":"Vaccine"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2269","DOI":"10.1080\/21645515.2019.1649532","article-title":"Recombinant vesicular stomatitis virus vector vaccines for WHO blueprint priority pathogens","volume":"15","author":"Fathi","year":"2019","journal-title":"Hum. Vaccin. Immunother."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"100009","DOI":"10.1016\/j.jvacx.2019.100009","article-title":"rVSV\u0394G-ZEBOV-GP (also designated V920) recombinant vesicular stomatitis virus pseudotyped with Ebola Zaire Glycoprotein: Standardized template with key considerations for a risk\/benefit assessment","volume":"1","author":"Monath","year":"2019","journal-title":"Vaccine X"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"7344","DOI":"10.1128\/JVI.78.14.7344-7351.2004","article-title":"Contribution of Ebola Virus Glycoprotein, Nucleoprotein, and VP24 to Budding of VP40 Virus-Like Particles","volume":"78","author":"Licata","year":"2004","journal-title":"J. Virol."},{"key":"ref_11","unstructured":"Murphy, F.A. (2025, May 25). Public Health Image Library, ID #10815, Available online: https:\/\/phil.cdc.gov\/details_linked.aspx?pid=10815."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Peng, W., Rayaprolu, V., Parvate, A.D., Pronker, M.F., Hui, S., Parekh, D., Shaffer, K., Yu, X., Saphire, E.O., and Snijder, J. (2022). Glycan shield of the ebolavirus envelope glycoprotein GP. Commun. Biol., 5.","DOI":"10.1038\/s42003-022-03767-1"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1128\/jvi.41.3.1055-1062.1982","article-title":"In Vitro Reassembly of Vesicular Stomatitis Virus Skeletons","volume":"41","author":"Newcomb","year":"1981","journal-title":"J. Virol."},{"key":"ref_14","unstructured":"Klenk, H.D., and Feldmann, H. (2003). Ebola and Marburg Viruses, Taylor & Francis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2263","DOI":"10.1007\/s007050170001","article-title":"Structural dynamics, an intrinsic property of viral capsids","volume":"146","author":"Witz","year":"2001","journal-title":"Arch. Virol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1007\/978-3-031-65187-8_18","article-title":"Mechanical Properties of Viruses","volume":"105","author":"Mateu","year":"2024","journal-title":"Sub-Cell. Biochem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"031914","DOI":"10.1103\/PhysRevE.78.031914","article-title":"Elastic modulus of viral nanotubes","volume":"78","author":"Zhao","year":"2008","journal-title":"Phys. Rev. E"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Magazzu, A., and Marcuello, C. (2023). Investigation of Soft Matter Nanomechanics by Atomic Force Microscopy and Optical Tweezers: A Comprehensive Review. Nanomaterials, 13.","DOI":"10.3390\/nano13060963"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Nonn, A., Kiss, B., Pezeshkian, W., Tancogne-Dejean, T., Cerrone, A., Kellermayer, M., Bai, Y., Li, W., and Wierzbicki, T. (2023). Inferring mechanical properties of the SARS-CoV-2 virus particle with nano-indentation tests and numerical simulations. J. Mech. Behav. Biomed. Mater., 148.","DOI":"10.1016\/j.jmbbm.2023.106153"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"S934","DOI":"10.1093\/infdis\/jir320","article-title":"Role of VP30 Phosphorylation in the Ebola Virus Replication Cycle","volume":"204","author":"Martinez","year":"2011","journal-title":"J. Inf. Dis."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1073\/pnas.0708057105","article-title":"Generation of biologically contained Ebola viruses","volume":"105","author":"Halfmann","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.cell.2020.03.011","article-title":"A Vaccine against Ebola Virus","volume":"181","author":"Saphire","year":"2020","journal-title":"Cell"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Garbutt, M., Liebscher, R., Wahl-Jensen, V., Jones, S., Moller, P., Wagner, R., Volchkov, V., Klenk, H.D., Feldmann, H., and Stroher, U. (2004). Properties of Replication-Competent Vesicular Stomatitus Virsu Vectors Expressing Glycoproteins of Filoviruses and Arenaviruses. J. Virol., 78.","DOI":"10.1128\/JVI.78.10.5458-5465.2004"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1007\/978-1-4939-7116-9_4","article-title":"Production of Filivirus Glycoprotein-Pseudotyped Vesicular Stomatitis for Study of Filovirus Entry Mechanisms","volume":"1628","author":"Brouillette","year":"2017","journal-title":"Methods Mol. Bio."},{"key":"ref_25","unstructured":"(2025, February 06). Bruker AFM, TESP-V2. Available online: https:\/\/www.brukerafmprobes.com\/p-3843-tesp-v2.aspx?srsltid=AfmBOopOMaARYbMtZHXzdeOPb81yXlo1B-10J-T6SJ6nmiFkvc02ehn_."},{"key":"ref_26","unstructured":"(2025, February 06). Bruker AFM, PEAKFORCE-HIRS-F-A. Available online: https:\/\/www.brukerafmprobes.com\/p-3954-peakforce-hirs-f-a.aspx?srsltid=AfmBOorSeg35kYInQBjYGbSk0k9MaBIC__698bN0kJFimmPlIfdMRj6r."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.ymeth.2021.06.011","article-title":"High resolution imaging of viruses: Scanning probe microscopy and related techniques","volume":"197","author":"Akhmetova","year":"2021","journal-title":"Methods"},{"key":"ref_28","first-page":"340","article-title":"Nanoindentation of Isometric Viruses on Deterministically Corrugated Substrates","volume":"120","author":"Zeng","year":"2015","journal-title":"J. Phys. Chem. B"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"6408","DOI":"10.1128\/JVI.76.12.6408-6412.2002","article-title":"Pre- and Postexposure Prophylaxis of Ebola Virus Infection in an Animal Model by Passive Transfer of a Neutralizing Human Antibody","volume":"76","author":"Parren","year":"2002","journal-title":"J. Virol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1641","DOI":"10.1021\/acs.nanolett.1c04677","article-title":"Stepwise Enzymatic-Dependent Mechanism of Ebola Virus Binding to Cell Surface Receptors Monitored by AFM","volume":"22","author":"Zhang","year":"2022","journal-title":"Nano Lett."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1021\/acs.nanolett.0c04609","article-title":"Single-Virus Force Spectroscopy Discriminates the Intrinsic Role of Two Viral Glycoproteins upon Cell Surface Attachment","volume":"21","author":"Delguste","year":"2021","journal-title":"Nano Lett."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1590","DOI":"10.1021\/acsinfecdis.3c00622","article-title":"Ebola Virus Glycoprotein Strongly Binds to Membranes in the Absence of Receptor Engagement","volume":"10","author":"Vaknin","year":"2024","journal-title":"ACS Infect. Dis."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"L14","DOI":"10.1529\/biophysj.106.084434","article-title":"Probing the Double Layer: Effect of Image Forces on AFM","volume":"91","author":"Sachs","year":"2006","journal-title":"Biophys. 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