Nicolas Mateos, Enric Gutierrez-Martinez, Jessica Angulo-Capel, Irene Carlon-Andres, Sergi Padilla-Parra, Maria F. Garcia-Parajo* and Juan A. Torreno-Pina*,
{"title":"活细胞中的高密度多色量子点图谱剖析单个多受体病毒相互作用的早期步骤","authors":"Nicolas Mateos, Enric Gutierrez-Martinez, Jessica Angulo-Capel, Irene Carlon-Andres, Sergi Padilla-Parra, Maria F. Garcia-Parajo* and Juan A. Torreno-Pina*, ","doi":"10.1021/acsnano.4c0908510.1021/acsnano.4c09085","DOIUrl":null,"url":null,"abstract":"<p >Viral capture and entry to target cells are the first crucial steps that ultimately lead to viral infection. Understanding these events is essential toward the design and development of suitable antiviral drugs and/or vaccines. Viral capture involves dynamic interactions of the virus with specific receptors in the plasma membrane of the target cells. In the last years, single virus tracking has emerged as a powerful approach to assess real time dynamics of viral processes in living cells and their engagement with specific cellular components. However, direct visualization of the early steps of multireceptor viral interactions at the single level has been largely impeded by the technical challenges associated with imaging individual multimolecular systems at relevant spatial (nanometer) and temporal (millisecond) scales. Here, we present a four-color, high-density quantum dot spatiotemporal mapping methodology to capture real-time interactions between individual virus-like-particles (VLPs) and three different viral (co-) receptors on the membrane of primary living immune cells derived from healthy donors. Together with quantitative tools, our approach revealed the existence of a coordinated spatiotemporal diffusion of the three different (co)receptors prior to viral engagement. By varying the temporal-windows of cumulated single-molecule localizations, we discovered that such a concerted diffusion impacts on the residence time of HIV-1 and SARS-CoV-2 VLPs on the host membrane and potential viral infectivity. Overall, our methodology offers the possibility for systematic analysis of the initial steps of viral-host interactions and could be easily implemented for the investigation of other multimolecular systems at the single-molecule level.</p>","PeriodicalId":21,"journal":{"name":"ACS Nano","volume":"18 42","pages":"28881–28893 28881–28893"},"PeriodicalIF":16.0000,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acsnano.4c09085","citationCount":"0","resultStr":"{\"title\":\"Early Steps of Individual Multireceptor Viral Interactions Dissected by High-Density, Multicolor Quantum Dot Mapping in Living Cells\",\"authors\":\"Nicolas Mateos, Enric Gutierrez-Martinez, Jessica Angulo-Capel, Irene Carlon-Andres, Sergi Padilla-Parra, Maria F. Garcia-Parajo* and Juan A. Torreno-Pina*, \",\"doi\":\"10.1021/acsnano.4c0908510.1021/acsnano.4c09085\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p >Viral capture and entry to target cells are the first crucial steps that ultimately lead to viral infection. Understanding these events is essential toward the design and development of suitable antiviral drugs and/or vaccines. Viral capture involves dynamic interactions of the virus with specific receptors in the plasma membrane of the target cells. In the last years, single virus tracking has emerged as a powerful approach to assess real time dynamics of viral processes in living cells and their engagement with specific cellular components. However, direct visualization of the early steps of multireceptor viral interactions at the single level has been largely impeded by the technical challenges associated with imaging individual multimolecular systems at relevant spatial (nanometer) and temporal (millisecond) scales. Here, we present a four-color, high-density quantum dot spatiotemporal mapping methodology to capture real-time interactions between individual virus-like-particles (VLPs) and three different viral (co-) receptors on the membrane of primary living immune cells derived from healthy donors. Together with quantitative tools, our approach revealed the existence of a coordinated spatiotemporal diffusion of the three different (co)receptors prior to viral engagement. By varying the temporal-windows of cumulated single-molecule localizations, we discovered that such a concerted diffusion impacts on the residence time of HIV-1 and SARS-CoV-2 VLPs on the host membrane and potential viral infectivity. 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Early Steps of Individual Multireceptor Viral Interactions Dissected by High-Density, Multicolor Quantum Dot Mapping in Living Cells
Viral capture and entry to target cells are the first crucial steps that ultimately lead to viral infection. Understanding these events is essential toward the design and development of suitable antiviral drugs and/or vaccines. Viral capture involves dynamic interactions of the virus with specific receptors in the plasma membrane of the target cells. In the last years, single virus tracking has emerged as a powerful approach to assess real time dynamics of viral processes in living cells and their engagement with specific cellular components. However, direct visualization of the early steps of multireceptor viral interactions at the single level has been largely impeded by the technical challenges associated with imaging individual multimolecular systems at relevant spatial (nanometer) and temporal (millisecond) scales. Here, we present a four-color, high-density quantum dot spatiotemporal mapping methodology to capture real-time interactions between individual virus-like-particles (VLPs) and three different viral (co-) receptors on the membrane of primary living immune cells derived from healthy donors. Together with quantitative tools, our approach revealed the existence of a coordinated spatiotemporal diffusion of the three different (co)receptors prior to viral engagement. By varying the temporal-windows of cumulated single-molecule localizations, we discovered that such a concerted diffusion impacts on the residence time of HIV-1 and SARS-CoV-2 VLPs on the host membrane and potential viral infectivity. Overall, our methodology offers the possibility for systematic analysis of the initial steps of viral-host interactions and could be easily implemented for the investigation of other multimolecular systems at the single-molecule level.
期刊介绍:
ACS Nano, published monthly, serves as an international forum for comprehensive articles on nanoscience and nanotechnology research at the intersections of chemistry, biology, materials science, physics, and engineering. The journal fosters communication among scientists in these communities, facilitating collaboration, new research opportunities, and advancements through discoveries. ACS Nano covers synthesis, assembly, characterization, theory, and simulation of nanostructures, nanobiotechnology, nanofabrication, methods and tools for nanoscience and nanotechnology, and self- and directed-assembly. Alongside original research articles, it offers thorough reviews, perspectives on cutting-edge research, and discussions envisioning the future of nanoscience and nanotechnology.