Dynamics of Receptor-Mediated Nanoparticle Internalization into Endothelial Cells
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{"title"=>"Dynamics of receptor-mediated nanoparticle internalization into endothelial cells", "type"=>"journal", "authors"=>[{"first_name"=>"David", "last_name"=>"Gonzalez-Rodriguez", "scopus_author_id"=>"57188589054"}, {"first_name"=>"Abdul I.", "last_name"=>"Barakat", "scopus_author_id"=>"7103227832"}], "year"=>2015, "source"=>"PLoS ONE", "identifiers"=>{"pmid"=>"25901833", "sgr"=>"84930640863", "doi"=>"10.1371/journal.pone.0122097", "scopus"=>"2-s2.0-84930640863", "pui"=>"604612314", "issn"=>"19326203"}, "id"=>"3e119642-e81c-33ce-bb1b-eb109714cf72", "abstract"=>"Nanoparticles offer a promising medical tool for targeted drug delivery, for example to treat inflamed endothelial cells during the development of atherosclerosis. To inform the design of such therapeutic strategies, we develop a computational model of nanoparticle internalization into endothelial cells, where internalization is driven by receptor-ligand binding and limited by the deformation of the cell membrane and cytoplasm. We specifically consider the case of nanoparticles targeted against ICAM-1 receptors, of relevance for treating atherosclerosis. The model computes the kinetics of the internalization process, the dynamics of binding, and the distribution of stresses exerted between the nanoparticle and the cell membrane. The model predicts the existence of an optimal nanoparticle size for fastest internalization, consistent with experimental observations, as well as the role of bond characteristics, local cell mechanical properties, and external forces in the nanoparticle internalization process.", "link"=>"http://www.mendeley.com/research/dynamics-receptormediated-nanoparticle-internalization-endothelial-cells", "reader_count"=>17, "reader_count_by_academic_status"=>{"Researcher"=>3, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>8, "Student > Postgraduate"=>1, "Student > Master"=>4}, "reader_count_by_user_role"=>{"Researcher"=>3, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>8, "Student > Postgraduate"=>1, "Student > Master"=>4}, "reader_count_by_subject_area"=>{"Engineering"=>6, "Biochemistry, Genetics and Molecular Biology"=>1, "Agricultural and Biological Sciences"=>3, "Pharmacology, Toxicology and Pharmaceutical Science"=>2, "Physics and Astronomy"=>4, "Chemistry"=>1}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>6}, "Chemistry"=>{"Chemistry"=>1}, "Physics and Astronomy"=>{"Physics and Astronomy"=>4}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>3}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>2}}, "reader_count_by_country"=>{"Italy"=>1}, "group_count"=>1}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/2035359"], "description"=>"<p><b>a.</b> Time required for particle internalization (defined as the time required to reach <i>d</i>/(2<i>a</i>) = 1) as a function of the particle radius, <i>a</i>, for all parameter values (other than <i>a</i>) equal to their best estimate (<a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0122097#pone.0122097.t001\" target=\"_blank\">Table 1</a>). The circles indicate the cases for which computations have been performed, and the dashed line joins the circles to guide the eye. Below <i>a</i> = 30 nm and above <i>a</i> = 110 nm, internalization (<i>d</i>/(2<i>a</i>) = 1) is not reached. <b>b.</b> Maximum internalization depth, <i>d</i>/(2<i>a</i>), which the internalization process converges to at sufficiently long time. The gray horizontal line corresponds to <i>d</i>/(2<i>a</i>) = 1, which we define as the threshold above which the particle is considered to be internalized.</p>", "links"=>[], "tags"=>["dynamic", "nanoparticle internalization process", "cell membrane", "binding", "icam", "Endothelial Cells Nanoparticles offer", "atherosclerosi", "model"], "article_id"=>1391072, "categories"=>["Uncategorised"], "users"=>["David Gonzalez-Rodriguez", "Abdul I. Barakat"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0122097.g004", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_particle_size_/1391072", "title"=>"Effect of particle size.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-04-22 03:21:47"}
  • {"files"=>["https://ndownloader.figshare.com/files/2035372"], "description"=>"<p><b>a.</b> Schematic illustrating the geometric parameters used in the scaling arguments. <b>b.</b> Snapshot of the internalization geometry for a particle of radius <i>a</i> = 30 nm at the time when <i>d</i>/(2<i>a</i>) = 0.5. <b>c.</b> Snapshot of the internalization geometry for a particle of radius <i>a</i> = 300 nm at the time when <i>d</i>/(2<i>a</i>) = 0.5.</p>", "links"=>[], "tags"=>["dynamic", "nanoparticle internalization process", "cell membrane", "binding", "icam", "Endothelial Cells Nanoparticles offer", "atherosclerosi", "model"], "article_id"=>1391085, "categories"=>["Uncategorised"], "users"=>["David Gonzalez-Rodriguez", "Abdul I. Barakat"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0122097.g010", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Illustration_of_the_particle_wrapping_process_/1391085", "title"=>"Illustration of the particle wrapping process.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-04-22 03:21:47"}
  • {"files"=>["https://ndownloader.figshare.com/files/2035357"], "description"=>"<p><b>a.</b> Evolution of the particle internalization, measured by the depth-to-diameter ratio, <i>d</i>/(2<i>a</i>) (see inset), as a function of the elapsed non-dimensional time (one nondimensional time unit corresponds typically to one second). The computation is performed with <i>a</i> = 50 nm, </p><p></p><p></p><p><mi>K</mi>d</p><p><mo stretchy=\"false\">(</mo><mn>0</mn><mo stretchy=\"false\">)</mo></p><p></p><mo>/</mo><p><mi>K</mi>f</p><mo>=</mo><mn>0</mn><mo>.</mo><mn>01</mn><mi>μ</mi><p>m</p><p><mo>−</mo><mn>2</mn></p><p></p><p></p><p></p> and otherwise with the best estimate of the parameter values listed in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0122097#pone.0122097.t001\" target=\"_blank\">Table 1</a>. The horizontal dashed line corresponds to the value <i>d</i>/(2<i>a</i>) = 1, which is the threshold where we define a particle as internalized. Four snapshots of the internalization process, indicated on plot <b>a</b> by circle markers denoted by ‘b’ to ‘e’ and corresponding to times <i>t</i> = 5 ⋅ 10<sup>−3</sup>, <i>t</i> = 10<sup>−2</sup>, <i>t</i> = 2.0, and <i>t</i> = 10.0 s, respectively, are presented in the plots <b>b</b> to <b>e</b>. Each snapshot shows the instantaneous membrane shape (full line), the initial membrane shape (dashed line), the particle (gray shaded circle), and the bonds formed between the particle and the membrane (short color lines). The density of color lines is proportional to the bond density. Dark blue, cyan, green, and red lines correspond respectively to bonds that are strongly compressed (<i>l</i> < 0.9<i>λ</i>), slightly compressed (0.9<i>λ</i> ≤ <i>l</i> < <i>λ</i>), slightly stretched (<i>λ</i> < <i>l</i> ≤ 1.1<i>λ</i>), or strongly stretched (<i>l</i> > 1.1<i>λ</i>).<p></p>", "links"=>[], "tags"=>["dynamic", "nanoparticle internalization process", "cell membrane", "binding", "icam", "Endothelial Cells Nanoparticles offer", "atherosclerosi", "model"], "article_id"=>1391070, "categories"=>["Uncategorised"], "users"=>["David Gonzalez-Rodriguez", "Abdul I. Barakat"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0122097.g003", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Kinetics_of_nanoparticle_internalization_/1391070", "title"=>"Kinetics of nanoparticle internalization.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-04-22 03:21:47"}
  • {"files"=>["https://ndownloader.figshare.com/files/2035371"], "description"=>"<p>Schematics illustrating a simplified view of the geometry of early particle wrapping.</p>", "links"=>[], "tags"=>["dynamic", "nanoparticle internalization process", "cell membrane", "binding", "icam", "Endothelial Cells Nanoparticles offer", "atherosclerosi", "model"], "article_id"=>1391084, "categories"=>["Uncategorised"], "users"=>["David Gonzalez-Rodriguez", "Abdul I. Barakat"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0122097.g009", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Schematics_illustrating_a_simplified_view_of_the_geometry_of_early_particle_wrapping_/1391084", "title"=>"Schematics illustrating a simplified view of the geometry of early particle wrapping.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-04-22 03:21:47"}
  • {"files"=>["https://ndownloader.figshare.com/files/2035352"], "description"=>"<p>The dash-dotted line is the axis of rotational symmetry. Ligand density (<i>ξ</i><sub>l</sub>) and receptor density (<i>ξ</i><sub>r</sub>) are assumed comparable. Bond density (<i>ξ</i><sub>b</sub>) is a function of the curvilinear coordinate, <i>s</i>, and of time, <i>t</i>. The elevation of the particle center above the initial cell membrane position is denoted by <i>Z</i><sub>0</sub>(<i>t</i>). The membrane position is defined by its coordinates <i>R</i>(<i>s</i>, <i>t</i>) and <i>Z</i>(<i>s</i>, <i>t</i>).</p>", "links"=>[], "tags"=>["dynamic", "nanoparticle internalization process", "cell membrane", "binding", "icam", "Endothelial Cells Nanoparticles offer", "atherosclerosi", "model"], "article_id"=>1391066, "categories"=>["Uncategorised"], "users"=>["David Gonzalez-Rodriguez", "Abdul I. Barakat"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0122097.g001", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Side_view_of_our_conceptualization_of_the_receptor_mediated_internalization_process_/1391066", "title"=>"Side view of our conceptualization of the receptor-mediated internalization process.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-04-22 03:21:47"}
  • {"files"=>["https://ndownloader.figshare.com/files/2035366"], "description"=>"<p>Different marker shapes and colors correspond to different values of the membrane bending modulus <i>B</i> (in plot <b>a</b>), of the initial membrane tension <i>T</i><sub>0</sub> (in plot <b>b</b>), or of the cell’s Young’s modulus <i>E</i> (in plot <b>c</b>). In each plot, the black curve corresponds to the <i>best estimate</i> of the varied parameter (<i>B</i> = 10<sup>−19</sup> J, <i>T</i><sub>0</sub> = 30 pN/<i>μ</i>m, and <i>E</i> = 10<sup>3</sup> Pa, respectively). On each plot, all parameter values not indicated are taken equal to their best estimates (<a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0122097#pone.0122097.t001\" target=\"_blank\">Table 1</a>). The gray horizontal line indicates the internalization threshold, <i>d</i>/(2<i>a</i>) = 1.</p>", "links"=>[], "tags"=>["dynamic", "nanoparticle internalization process", "cell membrane", "binding", "icam", "Endothelial Cells Nanoparticles offer", "atherosclerosi", "model"], "article_id"=>1391079, "categories"=>["Uncategorised"], "users"=>["David Gonzalez-Rodriguez", "Abdul I. Barakat"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0122097.g007", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_cell_mechanical_properties_on_the_maximum_internalization_depth_as_a_function_of_the_particle_radius_a_/1391079", "title"=>"Effect of cell mechanical properties on the maximum internalization depth as a function of the particle radius, <i>a</i>.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-04-22 03:21:47"}
  • {"files"=>["https://ndownloader.figshare.com/files/2035375"], "description"=>"<p><b>a.</b> Dependence of the maximum internalization depth, <i>d</i>/(2<i>a</i>), on the membrane bending modulus <i>B</i>. This plot presents the results of <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0122097#pone.0122097.g007\" target=\"_blank\">Fig 7a</a>, here with the horizontal axis transformed into <i>a</i>/(<i>B</i>/<i>B</i><sub>ref</sub>), with <i>B</i><sub>ref</sub> ≡ 10<sup>−19</sup> J. <b>b.</b> Dependence of the maximum internalization depth, <i>d</i>/(2<i>a</i>), on the cell’s Young modulus <i>E</i>. This plot presents the results of <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0122097#pone.0122097.g007\" target=\"_blank\">Fig 7c</a>, here with the vertical axis scaled as (<i>d</i>/(2<i>a</i>))(<i>E</i>/<i>E</i><sub>ref</sub>)<sup>1/2</sup>, with <i>E</i><sub>ref</sub> ≡ 1000 Pa, and the figure presented in double logarithmic scale. The dashed line indicates the slope of the power law <i>d</i>/(2<i>a</i>) ∼ <i>a</i><sup>−1/2</sup>.</p>", "links"=>[], "tags"=>["dynamic", "nanoparticle internalization process", "cell membrane", "binding", "icam", "Endothelial Cells Nanoparticles offer", "atherosclerosi", "model"], "article_id"=>1391088, "categories"=>["Uncategorised"], "users"=>["David Gonzalez-Rodriguez", "Abdul I. Barakat"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0122097.g011", "stats"=>{"downloads"=>0, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Analysis_of_the_dependence_of_the_maximum_internalization_depth_on_physical_parameters_B_E_and_a_/1391088", "title"=>"Analysis of the dependence of the maximum internalization depth on physical parameters <i>B</i>, <i>E</i>, and <i>a</i>.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-04-22 03:21:47"}
  • {"files"=>["https://ndownloader.figshare.com/files/2035355"], "description"=>"<p>The membrane’s top face sustains a stress <i>σ</i><sub>b</sub> arising from bond deformation. The bonds behave as linear elastic springs of constant <i>κ</i> and undeformed length <i>λ</i>. In addition, if the membrane and the particle get very close, a short-range repulsion force (not represented in the figure) prevents particle-membrane interpenetration. The membrane’s bottom face sustains a stress arising from the viscoelastic deformation of the cell’s cytoplasm, which is modeled as a Kelvin-Voigt material of elastic constant <i>K</i> = <i>E</i>/<i>a</i> and viscous constant <i>M</i> = <i>μ</i>/<i>a</i>.</p>", "links"=>[], "tags"=>["dynamic", "nanoparticle internalization process", "cell membrane", "binding", "icam", "Endothelial Cells Nanoparticles offer", "atherosclerosi", "model"], "article_id"=>1391068, "categories"=>["Uncategorised"], "users"=>["David Gonzalez-Rodriguez", "Abdul I. Barakat"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0122097.g002", "stats"=>{"downloads"=>0, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Schematic_of_the_stresses_exerted_on_the_membrane_/1391068", "title"=>"Schematic of the stresses exerted on the membrane.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-04-22 03:21:47"}
  • {"files"=>["https://ndownloader.figshare.com/files/2035369"], "description"=>"<p><b>a.</b> Time required for particle internalization (defined as the time required to reach <i>d</i>/(2<i>a</i>) = 1) as a function of a normalized vertical compressive force, , for <i>a</i> = 50 nm and all other parameter values equal to their best estimates (<a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0122097#pone.0122097.t001\" target=\"_blank\">Table 1</a>). The inset shows a snapshot of the membrane deformation and particle position for the case </p><p></p><p></p><p></p><p><mi>F</mi><mo>^</mo></p>v<p></p><mo>=</mo><mo>−</mo><mn>1</mn><p></p><p></p>. The snapshot corresponds to the time when <i>d</i>/<i>a</i> = 1. <b>b.</b> Time required for particle internalization (defined as the time required to reach <i>d</i>/(2<i>a</i>) = 1) as a function of the particle radius <i>a</i> in the absence of force (black circles) and in the presence of a normalized force <p></p><p></p><p></p><p><mi>F</mi><mo>^</mo></p>v<p></p><mo>=</mo><mo>−</mo><mn>0</mn><mo>.</mo><mn>5</mn><p></p><p></p> (blue squares).<p></p>", "links"=>[], "tags"=>["dynamic", "nanoparticle internalization process", "cell membrane", "binding", "icam", "Endothelial Cells Nanoparticles offer", "atherosclerosi", "model"], "article_id"=>1391082, "categories"=>["Uncategorised"], "users"=>["David Gonzalez-Rodriguez", "Abdul I. Barakat"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0122097.g008", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_a_vertical_force_on_internalization_/1391082", "title"=>"Effect of a vertical force on internalization.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-04-22 03:21:47"}
  • {"files"=>["https://ndownloader.figshare.com/files/2035378"], "description"=>"<p>Nondimensional coefficients and typical values.</p>", "links"=>[], "tags"=>["dynamic", "nanoparticle internalization process", "cell membrane", "binding", "icam", "Endothelial Cells Nanoparticles offer", "atherosclerosi", "model"], "article_id"=>1391091, "categories"=>["Uncategorised"], "users"=>["David Gonzalez-Rodriguez", "Abdul I. Barakat"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0122097.t002", "stats"=>{"downloads"=>2, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Nondimensional_coefficients_and_typical_values_/1391091", "title"=>"Nondimensional coefficients and typical values.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-04-22 03:21:47"}
  • {"files"=>["https://ndownloader.figshare.com/files/2035363"], "description"=>"<p>Different marker shapes and colors correspond to different values of the bond spring constant <i>κ</i> (in plot <b>a</b>), of the bond reaction constant </p><p></p><p></p><p><mi>K</mi>d</p><p><mo stretchy=\"false\">(</mo><mn>0</mn><mo stretchy=\"false\">)</mo></p><p></p><mo>/</mo><p><mi>K</mi>f</p><p></p><p></p> (in plot <b>b</b>), or of the ligand density <i>ξ</i><sub>l</sub> (in plot <b>c</b>). In all plots, the black curve corresponds to the <i>best estimate</i> of the varied parameter (<i>κ</i> = 10<sup>−2</sup> N/m, <p></p><p></p><p><mi>K</mi>d</p><p><mo stretchy=\"false\">(</mo><mn>0</mn><mo stretchy=\"false\">)</mo></p><p></p><mo>/</mo><p><mi>K</mi>f</p><mo>=</mo><mn>5</mn><mo>⋅</mo><p><mn>10</mn></p><p><mo>−</mo><mn>2</mn></p><p></p><mi>μ</mi><p>m</p><p><mo>−</mo><mn>2</mn></p><p></p><p></p><p></p>, and <i>ξ</i><sub>l</sub> = 10<sup>3</sup><i>μ</i>m<sup>−2</sup>, respectively). In each plot, all parameter values not indicated are taken equal to their best estimates (<a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0122097#pone.0122097.t001\" target=\"_blank\">Table 1</a>), except for <i>ξ</i><sub>r</sub> = <i>ξ</i><sub>l</sub> in plot <b>c</b>. The gray horizontal line indicates the internalization threshold, <i>d</i>/(2<i>a</i>) = 1.<p></p>", "links"=>[], "tags"=>["dynamic", "nanoparticle internalization process", "cell membrane", "binding", "icam", "Endothelial Cells Nanoparticles offer", "atherosclerosi", "model"], "article_id"=>1391076, "categories"=>["Uncategorised"], "users"=>["David Gonzalez-Rodriguez", "Abdul I. Barakat"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0122097.g006", "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_bond_properties_on_the_maximum_internalization_depth_as_a_function_of_the_particle_radius_a_/1391076", "title"=>"Effect of bond properties on the maximum internalization depth as a function of the particle radius, <i>a</i>.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-04-22 03:21:47"}
  • {"files"=>["https://ndownloader.figshare.com/files/2035360"], "description"=>"<p>Both times are normalized by the viscoelastic time <i>μ</i>/<i>E</i>, and can be interpreted as given in seconds if <i>μ</i>/<i>E</i> = 1 s. The circles correspond to the computations, performed with parameter values (other than <i>a</i> = 50 nm and than <i>K</i><sub>f</sub>, which is variable since it determines <i>t</i><sub>b</sub>) equal to their best estimate (<a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0122097#pone.0122097.t001\" target=\"_blank\">Table 1</a>). The straight dashed line is a fit through the data points.</p>", "links"=>[], "tags"=>["dynamic", "nanoparticle internalization process", "cell membrane", "binding", "icam", "Endothelial Cells Nanoparticles offer", "atherosclerosi", "model"], "article_id"=>1391073, "categories"=>["Uncategorised"], "users"=>["David Gonzalez-Rodriguez", "Abdul I. Barakat"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0122097.g005", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Particle_internalization_time_as_a_function_of_the_bond_formation_time_t_b_/1391073", "title"=>"Particle internalization time as a function of the bond formation time, <i>t</i><sub>b</sub>.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-04-22 03:21:47"}
  • {"files"=>["https://ndownloader.figshare.com/files/2035377"], "description"=>"<p>Typical values of the model parameters.</p>", "links"=>[], "tags"=>["dynamic", "nanoparticle internalization process", "cell membrane", "binding", "icam", "Endothelial Cells Nanoparticles offer", "atherosclerosi", "model"], "article_id"=>1391090, "categories"=>["Uncategorised"], "users"=>["David Gonzalez-Rodriguez", "Abdul I. Barakat"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0122097.t001", "stats"=>{"downloads"=>2, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Typical_values_of_the_model_parameters_/1391090", "title"=>"Typical values of the model parameters.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-04-22 03:21:47"}

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  • {"unique-ip"=>"9", "full-text"=>"12", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"8"}
  • {"unique-ip"=>"7", "full-text"=>"7", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"10"}
  • {"unique-ip"=>"7", "full-text"=>"6", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"11"}
  • {"unique-ip"=>"8", "full-text"=>"8", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"12"}
  • {"unique-ip"=>"8", "full-text"=>"10", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"2"}
  • {"unique-ip"=>"6", "full-text"=>"5", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"3"}
  • {"unique-ip"=>"4", "full-text"=>"3", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"4"}
  • {"unique-ip"=>"5", "full-text"=>"5", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"5"}

Relative Metric

{"start_date"=>"2015-01-01T00:00:00Z", "end_date"=>"2015-12-31T00:00:00Z", "subject_areas"=>[]}
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