Effects of Plasma Membrane Cholesterol Level and Cytoskeleton F-Actin on Cell Protrusion Mechanics
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{"title"=>"Effects of Plasma Membrane Cholesterol Level and Cytoskeleton F-Actin on Cell Protrusion Mechanics", "type"=>"journal", "authors"=>[{"first_name"=>"Nima", "last_name"=>"Khatibzadeh", "scopus_author_id"=>"14822363600"}, {"first_name"=>"Alexander A.", "last_name"=>"Spector", "scopus_author_id"=>"7203039214"}, {"first_name"=>"William E.", "last_name"=>"Brownell", "scopus_author_id"=>"7006844559"}, {"first_name"=>"Bahman", "last_name"=>"Anvari", "scopus_author_id"=>"7005435744"}], "year"=>2013, "source"=>"PLoS ONE", "identifiers"=>{"scopus"=>"2-s2.0-84874292780", "pmid"=>"23451167", "sgr"=>"84874292780", "doi"=>"10.1371/journal.pone.0057147", "isbn"=>"1932-6203 (Electronic)\\n1932-6203 (Linking)", "issn"=>"19326203", "pui"=>"368409641"}, "id"=>"0d3bbe9a-4ff4-36ae-9380-6d56bf064129", "abstract"=>"Protrusions are deformations that form at the surface of living cells during biological activities such as cell migration. Using combined optical tweezers and fluorescent microscopy, we quantified the mechanical properties of protrusions in adherent human embryonic kidney cells in response to application of an external force at the cell surface. The mechanical properties of protrusions were analyzed by obtaining the associated force-length plots during protrusion formation, and force relaxation at constant length. Protrusion mechanics were interpretable by a standard linear solid (Kelvin) model, consisting of two stiffness parameters, k0 and k1 (with k0>k1), and a viscous coefficient. While both stiffness parameters contribute to the time-dependant mechanical behavior of the protrusions, k0 and k1 in particular dominated the early and late stages of the protrusion formation and elongation process, respectively. Lowering the membrane cholesterol content by 25% increased the k0 stiffness by 74%, and shortened the protrusion length by almost half. Enhancement of membrane cholesterol content by nearly two-fold increased the protrusion length by 30%, and decreased the k0 stiffness by nearly two-and-half-fold as compared with control cells. Cytoskeleton integrity was found to make a major contribution to protrusion mechanics as evidenced by the effects of F-actin disruption on the resulting mechanical parameters. Viscoelastic behavior of protrusions was further characterized by hysteresis and force relaxation after formation. The results of this study elucidate the coordination of plasma membrane composition and cytoskeleton during protrusion formation.", "link"=>"http://www.mendeley.com/research/effects-plasma-membrane-cholesterol-level-cytoskeleton-factin-cell-protrusion-mechanics", "reader_count"=>52, "reader_count_by_academic_status"=>{"Unspecified"=>3, "Professor > Associate Professor"=>4, "Student > Doctoral Student"=>2, "Researcher"=>9, "Student > Ph. D. Student"=>16, "Student > Postgraduate"=>2, "Student > Master"=>6, "Other"=>1, "Student > Bachelor"=>5, "Lecturer > Senior Lecturer"=>1, "Professor"=>3}, "reader_count_by_user_role"=>{"Unspecified"=>3, "Professor > Associate Professor"=>4, "Student > Doctoral Student"=>2, "Researcher"=>9, "Student > Ph. D. Student"=>16, "Student > Postgraduate"=>2, "Student > Master"=>6, "Other"=>1, "Student > Bachelor"=>5, "Lecturer > Senior Lecturer"=>1, "Professor"=>3}, "reader_count_by_subject_area"=>{"Unspecified"=>3, "Agricultural and Biological Sciences"=>19, "Business, Management and Accounting"=>1, "Chemical Engineering"=>1, "Chemistry"=>3, "Decision Sciences"=>1, "Engineering"=>4, "Biochemistry, Genetics and Molecular Biology"=>2, "Materials Science"=>1, "Medicine and Dentistry"=>3, "Neuroscience"=>4, "Physics and Astronomy"=>8, "Social Sciences"=>1, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Materials Science"=>{"Materials Science"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>3}, "Social Sciences"=>{"Social Sciences"=>1}, "Decision Sciences"=>{"Decision Sciences"=>1}, "Physics and Astronomy"=>{"Physics and Astronomy"=>8}, "Unspecified"=>{"Unspecified"=>3}, "Chemical Engineering"=>{"Chemical Engineering"=>1}, "Engineering"=>{"Engineering"=>4}, "Chemistry"=>{"Chemistry"=>3}, "Neuroscience"=>{"Neuroscience"=>4}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>19}, "Business, Management and Accounting"=>{"Business, Management and Accounting"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>2}}, "reader_count_by_country"=>{"France"=>1, "Chile"=>1}, "group_count"=>1}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/969070"], "description"=>"<p>Dashed lines show initial cell-bead contact where there is no external force applied on the bead. Solid lines show the bead-cell system once the cell is moved away from the trapped bead by distance <i>x</i><sub>pzt</sub>. Bead is displaced from the trapping center by <i>x</i><sub>bead</sub> and the length of the protrusion is <i>x</i><sub>pt</sub>.</p>", "links"=>[], "tags"=>["bead-cell"], "article_id"=>638490, "categories"=>["Physics", "Biotechnology", "Biochemistry", "Cell Biology", "Biophysics"], "users"=>["Nima Khatibzadeh", "Alexander A. Spector", "William E. Brownell", "Bahman Anvari"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0057147.g002", "stats"=>{"downloads"=>1, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Schematic_of_bead_cell_contact_system_/638490", "title"=>"Schematic of bead-cell contact system.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-23 12:05:08"}
  • {"files"=>["https://ndownloader.figshare.com/files/969082"], "description"=>"<p>Effect of membrane cholesterol content on: (<b>A</b>) stiffness parameter <i>k</i><sub>0</sub>, and (<b>B</b>) stiffness parameter <i>k</i><sub>1</sub> for cells with intact or disrupted F-actin.</p>", "links"=>[], "tags"=>["cell biology", "biotechnology", "biophysics", "physics", "Biochemistry"], "article_id"=>638502, "categories"=>["Physics", "Biotechnology", "Biochemistry", "Cell Biology", "Biophysics"], "users"=>["Nima Khatibzadeh", "Alexander A. Spector", "William E. Brownell", "Bahman Anvari"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0057147.g007", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Protrusion_stiffness_/638502", "title"=>"Protrusion stiffness.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-23 12:06:52"}
  • {"files"=>["https://ndownloader.figshare.com/files/969079"], "description"=>"<p>Maximum length of protrusion (<i>l</i><sub>pt-max</sub>) is defined the length at which the membrane becomes separated from the cytoskeleton.</p>", "links"=>[], "tags"=>["membrane", "cytoskeletal", "f-actin", "protrusion"], "article_id"=>638499, "categories"=>["Physics", "Biotechnology", "Biochemistry", "Cell Biology", "Biophysics"], "users"=>["Nima Khatibzadeh", "Alexander A. Spector", "William E. Brownell", "Bahman Anvari"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0057147.g006", "stats"=>{"downloads"=>1, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_membrane_cholesterol_content_and_cytoskeletal_F_actin_on_maximum_protrusion_length_/638499", "title"=>"Effect of membrane cholesterol content and cytoskeletal F-actin on maximum protrusion length.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-23 12:06:37"}
  • {"files"=>["https://ndownloader.figshare.com/files/1005223"], "description"=>"<p>Plasma membrane cholesterol concentration in control cells is 7.54 pmol/µg protein. Lat-A represents treatment of the cells with Latrunculin-A in order to disrupt F-actin polymerization.</p>¶<p>Membrane tether effective viscosity was not determined at 5.68 pmol/µg protein cholesterol concentration, but its value under cholesterol depleted conditions at 6.6±0.3 pmol/µg protein was ≈2.1±0.4 pN.s/µm <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0057147#pone.0057147-Khatibzadeh1\" target=\"_blank\">[13]</a>.</p>", "links"=>[], "tags"=>["membrane", "protrusion", "stiffness"], "article_id"=>665844, "categories"=>["Physics", "Biotechnology", "Biochemistry", "Cell Biology", "Biophysics"], "users"=>["Nima Khatibzadeh", "Alexander A. Spector", "William E. Brownell", "Bahman Anvari"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0057147.t001", "stats"=>{"downloads"=>0, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Plasma_membrane_and_protrusion_stiffness_and_viscosity_/665844", "title"=>"Plasma membrane and protrusion stiffness and viscosity.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-22 01:37:24"}
  • {"files"=>["https://ndownloader.figshare.com/files/969078"], "description"=>"<p>Maximum protrusion force (<i>F</i><sub>max</sub>) is defined as the force that results in separation of membrane from cytoskeleton.</p>", "links"=>[], "tags"=>["membrane", "cytoskeletal", "f-actin", "protrusion"], "article_id"=>638498, "categories"=>["Physics", "Biotechnology", "Biochemistry", "Cell Biology", "Biophysics"], "users"=>["Nima Khatibzadeh", "Alexander A. Spector", "William E. Brownell", "Bahman Anvari"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0057147.g005", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_membrane_cholesterol_content_and_cytoskeletal_F_actin_on_maximum_protrusion_force_/638498", "title"=>"Effect of membrane cholesterol content and cytoskeletal F-actin on maximum protrusion force.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-23 12:06:32"}
  • {"files"=>["https://ndownloader.figshare.com/files/969092"], "description"=>"<p>(<b>A</b>) Effect of membrane cholesterol content on the percent of energy loss associated with protrusion hysteresis for intact and disrupted F-actin cells. (<b>B</b>) Force-length plots indicating hysteresis in cells with intact and disrupted F-actin. lpar;<b>C</b>) Protrusion force during protrusion elongation to 3 µm (time interval D–E) followed by force relaxation after the protrusion reaches 3 µm, and maintained at that length (time interval E–F). The interval F–G displays the force as the protrusion is unloaded (pushed back). The inset shows the SLS-fit to the force relaxation during the time interval between the end of the pulling time and beginning of the pushing time (E–F). The general solution for the protrusion force relaxation under constant length is: , where <i>x</i><sub>pt</sub> is the constant length of the protrusion (3 µm), and <i>F</i><sub>0</sub> is the force at the beginning of relaxation. The ∼7 seconds time interval between zero second and point D indicates bead-cell contact prior to the push-pull experiments beginning at D.</p>", "links"=>[], "tags"=>["protrusion"], "article_id"=>638511, "categories"=>["Physics", "Biotechnology", "Biochemistry", "Cell Biology", "Biophysics"], "users"=>["Nima Khatibzadeh", "Alexander A. Spector", "William E. Brownell", "Bahman Anvari"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0057147.g009", "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Energy_loss_associated_with_protrusion_hysteresis_/638511", "title"=>"Energy loss associated with protrusion hysteresis.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-23 12:07:50"}
  • {"files"=>["https://ndownloader.figshare.com/files/969073"], "description"=>"<p>(<b>A</b>) Standard linear solid (SLS) model of the protrusion. The model includes a Maxwell arm (viscous coefficient of <i>η<sub>0</sub></i> in series with spring with stiffness <i>k</i><sub>0</sub>) in parallel with a spring with stiffness <i>k</i><sub>1</sub>. (<b>B</b>) Two illustrative force-length profiles of protrusion elongation fitted with the SLS model (blue solid lines). The red circles show data for a cell with intact F-actin and normal membrane cholesterol content. Data in black circles are from cells with disrupted F-actin using Latrunculin-A, but with and normal membrane cholesterol level.</p>", "links"=>[], "tags"=>["protrusions", "viscoelastic"], "article_id"=>638493, "categories"=>["Physics", "Biotechnology", "Biochemistry", "Cell Biology", "Biophysics"], "users"=>["Nima Khatibzadeh", "Alexander A. Spector", "William E. Brownell", "Bahman Anvari"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0057147.g003", "stats"=>{"downloads"=>1, "page_views"=>32, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Cell_protrusions_as_a_viscoelastic_structure_/638493", "title"=>"Cell protrusions as a viscoelastic structure.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-23 12:05:43"}
  • {"files"=>["https://ndownloader.figshare.com/files/969069"], "description"=>"<p>The protrusion forms in response to application of a tensile force (<i>F</i>) on the cell surface in <i>y</i> direction by a laser trapped microsphere (bead) (drawn not to scale). A quadrant photodetector records the instantaneous displacement of the trapped microsphere from the trapping center for force measurements while the stage is driven in the negative <i>y</i> direction.</p>", "links"=>[], "tags"=>["protrusion", "induced", "adherent", "optical"], "article_id"=>638489, "categories"=>["Physics", "Biotechnology", "Biochemistry", "Cell Biology", "Biophysics"], "users"=>["Nima Khatibzadeh", "Alexander A. Spector", "William E. Brownell", "Bahman Anvari"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0057147.g001", "stats"=>{"downloads"=>0, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Schematic_of_a_protrusion_induced_on_an_adherent_living_cell_using_optical_tweezers_/638489", "title"=>"Schematic of a protrusion induced on an adherent living cell using optical tweezers.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-23 12:04:57"}
  • {"files"=>["https://ndownloader.figshare.com/files/969086"], "description"=>"<p>Effect of membrane cholesterol content on the viscosity coefficient of the protrusion for cells with intact or disrupted F-actin. Asterisk (*) indicates a statistically significant difference with control; ** indicates a statistically significant difference between the two indicated data sets; and + indicates a statistically significant difference between intact F-actin and F-actin disrupted cells at the same cholesterol concentration.</p>", "links"=>[], "tags"=>["cell biology", "biotechnology", "biophysics", "physics", "Biochemistry"], "article_id"=>638506, "categories"=>["Physics", "Biotechnology", "Biochemistry", "Cell Biology", "Biophysics"], "users"=>["Nima Khatibzadeh", "Alexander A. Spector", "William E. Brownell", "Bahman Anvari"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0057147.g008", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Protrusion_viscosity_/638506", "title"=>"Protrusion viscosity.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-23 12:07:24"}
  • {"files"=>["https://ndownloader.figshare.com/files/969096", "https://ndownloader.figshare.com/files/969101", "https://ndownloader.figshare.com/files/969108", "https://ndownloader.figshare.com/files/969109", "https://ndownloader.figshare.com/files/969111", "https://ndownloader.figshare.com/files/969114", "https://ndownloader.figshare.com/files/969118", "https://ndownloader.figshare.com/files/969123"], "description"=>"<div><p>Protrusions are deformations that form at the surface of living cells during biological activities such as cell migration. Using combined optical tweezers and fluorescent microscopy, we quantified the mechanical properties of protrusions in adherent human embryonic kidney cells in response to application of an external force at the cell surface. The mechanical properties of protrusions were analyzed by obtaining the associated force-length plots during protrusion formation, and force relaxation at constant length. Protrusion mechanics were interpretable by a standard linear solid (Kelvin) model, consisting of two stiffness parameters, <i>k</i><sub>0</sub> and <i>k</i><sub>1</sub> (with <i>k</i><sub>0</sub>><i>k</i><sub>1</sub>), and a viscous coefficient. While both stiffness parameters contribute to the time-dependant mechanical behavior of the protrusions, <i>k</i><sub>0</sub> and <i>k</i><sub>1</sub> in particular dominated the early and late stages of the protrusion formation and elongation process, respectively. Lowering the membrane cholesterol content by 25% increased the <i>k</i><sub>0</sub> stiffness by 74%, and shortened the protrusion length by almost half. Enhancement of membrane cholesterol content by nearly two-fold increased the protrusion length by 30%, and decreased the <i>k</i><sub>0</sub> stiffness by nearly two-and-half-fold as compared with control cells. Cytoskeleton integrity was found to make a major contribution to protrusion mechanics as evidenced by the effects of F-actin disruption on the resulting mechanical parameters. Viscoelastic behavior of protrusions was further characterized by hysteresis and force relaxation after formation. The results of this study elucidate the coordination of plasma membrane composition and cytoskeleton during protrusion formation.</p> </div>", "links"=>[], "tags"=>["plasma", "membrane", "cytoskeleton", "f-actin", "protrusion", "mechanics"], "article_id"=>638515, "categories"=>["Physics", "Biotechnology", "Biochemistry", "Cell Biology", "Biophysics"], "users"=>["Nima Khatibzadeh", "Alexander A. Spector", "William E. Brownell", "Bahman Anvari"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0057147.s001", "https://dx.doi.org/10.1371/journal.pone.0057147.s002", "https://dx.doi.org/10.1371/journal.pone.0057147.s003", "https://dx.doi.org/10.1371/journal.pone.0057147.s004", "https://dx.doi.org/10.1371/journal.pone.0057147.s005", "https://dx.doi.org/10.1371/journal.pone.0057147.s006", "https://dx.doi.org/10.1371/journal.pone.0057147.s007", "https://dx.doi.org/10.1371/journal.pone.0057147.s008"], "stats"=>{"downloads"=>7, "page_views"=>35, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Effects_of_Plasma_Membrane_Cholesterol_Level_and_Cytoskeleton_F_Actin_on_Cell_Protrusion_Mechanics__/638515", "title"=>"Effects of Plasma Membrane Cholesterol Level and Cytoskeleton F-Actin on Cell Protrusion Mechanics", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2013-02-23 12:08:25"}
  • {"files"=>["https://ndownloader.figshare.com/files/969077"], "description"=>"<p>An example force-time plot involving subsequent “pull” and “push” processes. The ∼1 second time interval between zero second and point A indicates bead-cell contact prior to the push-pull experiments beginning at A.</p>", "links"=>[], "tags"=>["cell biology", "biotechnology", "biophysics", "physics", "Biochemistry"], "article_id"=>638497, "categories"=>["Physics", "Biotechnology", "Biochemistry", "Cell Biology", "Biophysics"], "users"=>["Nima Khatibzadeh", "Alexander A. Spector", "William E. Brownell", "Bahman Anvari"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0057147.g004", "stats"=>{"downloads"=>1, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Reverse_pull_experiment_/638497", "title"=>"Reverse pull experiment.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-23 12:06:25"}

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Relative Metric

{"start_date"=>"2013-01-01T00:00:00Z", "end_date"=>"2013-12-31T00:00:00Z", "subject_areas"=>[{"subject_area"=>"/Physical sciences/Materials science", "average_usage"=>[250, 417, 535, 649, 758, 857, 952, 1036, 1113, 1206, 1287, 1353, 1429]}, {"subject_area"=>"/Physical sciences/Physics", "average_usage"=>[254, 421, 527, 626, 720, 813, 900, 983, 1063, 1136, 1210, 1283, 1342]}]}
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