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<option value="abstract">Abstract</option>
<option value="abstract-text">Abstract (text)</option>
</select>
</div>
<div class="include-supplemental-container">
<input type="checkbox" aria-label="Include MeSH and other data" name="include-supplemental" id="email-include-supplemental" class="email-include-supplemental">
<label for="email-include-supplemental" class="email-include-supplemental-label">MeSH and other data</label>
</div>
<div class="form-field recaptcha ">
<div class="g-recaptcha" id="id-recaptcha" data-sitekey="6LfsWHMdAAAAAClKbtOpjQ2pMjgsGxvv7NdZW9uI"></div>
</div>
<div id="captcha-error-message" class="usa-input-error-message captcha-validation-message" role="alert"></div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Sending..."
data-ga-category="save_share"
data-ga-action="email"
data-ga-label="send">
Send email
</button>
<button class="action-panel-cancel"
aria-label="Close 'Email citations' panel"
ref="linksrc=close_email_panel"
aria-controls="email-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="email"
data-ga-label="cancel">
Cancel
</button>
</div>
<input type="hidden" name="email-search-details" value="" />
<input type="hidden" name="email-search-details-hash" value="0e42663a6c3bd85498fcb88798998fed7bfdc45d457db35281e41afe13cc0524" />
</form>
</div>
</div>
<div id="collections-action-panel"
class="collections-action-panel action-panel in-progress-dots-panel"
aria-hidden="true"
data-collections-open-panel-enabled="false"
data-collections-open-panel-url-hash="#open-collections-panel">
<div class="inner-wrap">
<h3 class="action-panel-heading">
Add to Collections
</h3>
<form id="collections-action-panel-form"
class="collections-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
data-existing-collections-url="/list-existing-collections/"
data-add-to-existing-collection-url="/add-to-existing-collection/"
data-create-and-add-to-new-collection-url="/create-and-add-to-new-collection/"
data-get-article-ids-by-search-url="/get-article-ids-by-search/"
data-myncbi-max-collection-name-length="100"
data-add-to-collection-max-amount="1000"
data-collections-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/">
<input type="hidden" name="csrfmiddlewaretoken" value="CJRrPPqtWM7A6xorlcWQFix5Wz5P6chdTwBwsFTPwnU40YuhYvzS9q3JuDN1ZNPx">
<div class="choice-group" role="radiogroup">
<ul class="radio-group-items">
<li>
<input type="radio"
id="collections-action-panel-new"
class="collections-new"
name="collections"
value="new"
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="collections_radio_new">
<label for="collections-action-panel-new">Create a new collection</label>
</li>
<li>
<input type="radio"
id="collections-action-panel-existing"
class="collections-existing"
name="collections"
value="existing"
checked="true"
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="collections_radio_existing">
<label for="collections-action-panel-existing">Add to an existing collection</label>
</li>
</ul>
</div>
<div class="controls-wrapper">
<div class="action-panel-control-wrap new-collections-controls">
<label for="collections-action-panel-add-to-new" class="action-panel-label required-field-asterisk">
Name your collection:
</label>
<input
type="text"
name="add-to-new-collection"
id="collections-action-panel-add-to-new"
class="collections-action-add-to-new"
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/"
maxlength="100"
data-ga-category="save_share"
data-ga-action="create_collection"
data-ga-label="non_favorties_collection">
<div class="collections-new-name-too-long usa-input-error-message selection-validation-message">
Name must be less than 100 characters
</div>
</div>
<div class="action-panel-control-wrap existing-collections-controls">
<label for="collections-action-panel-add-to-existing" class="action-panel-label">
Choose a collection:
</label>
<select id="collections-action-panel-add-to-existing"
class="action-panel-selector collections-action-add-to-existing"
data-ga-category="save_share"
data-ga-action="select_collection"
data-ga-label="($('#collections-action-add-to-existing').val() === 'Favorites') ? 'Favorites' : 'non_favorites_collection'">
</select>
<div class="collections-retry-load-on-error usa-input-error-message selection-validation-message">
Unable to load your collection due to an error<br>
<a href="#">Please try again</a>
</div>
</div>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Adding..."
data-pinger-ignore
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="add">
Add
</button>
<button class="action-panel-cancel"
aria-label="Close 'Add to Collections' panel"
ref="linksrc=close_collections_panel"
aria-controls="collections-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="bibliography-action-panel"
class="bibliography-action-panel action-panel in-progress-dots-panel"
aria-hidden="true"
data-bibliography-open-panel-enabled="false"
data-bibliography-open-panel-url-hash="#open-bibliography-panel">
<div class="inner-wrap">
<h3 class="action-panel-heading">
Add to My Bibliography
</h3>
<form id="bibliography-action-panel-form"
class="bibliography-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
data-add-to-bibliography-max-amount="100"
data-add-to-bibliography-batch-size="10"
data-bibliography-delegates-url="/list-bibliography-delegates/"
data-add-to-bibliography-url="/add-to-bibliography/"
data-get-article-ids-by-search-url="/get-article-ids-by-search/"
data-mybib-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/mybibliography/">
<input type="hidden" name="csrfmiddlewaretoken" value="CJRrPPqtWM7A6xorlcWQFix5Wz5P6chdTwBwsFTPwnU40YuhYvzS9q3JuDN1ZNPx">
<div class="action-panel-control-wrap bibliographies-controls">
<div class="choice-group">
<ul class="bibliographies-action-add radio-group-items">
<li>
<input name="bibliography" id="my-bibliography" class="my-bibliography" type="radio" checked/>
<label for="my-bibliography">My Bibliography</label>
</li>
</ul>
</div>
</div>
<div class="bibliographies-retry-load-on-error usa-input-error-message selection-validation-message">
Unable to load your delegates due to an error<br>
<a href="#">Please try again</a>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Adding..."
data-pinger-ignore>
Add
</button>
<button class="action-panel-cancel"
aria-label="Close 'Add to bibliography' panel"
ref="linksrc=close_bibliography_panel"
aria-controls="bibliography-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="mybib"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="saved-search-action-panel" class="saved-search-action-panel action-panel " aria-hidden="true"
data-saved-search-open-panel-enabled="false"
data-saved-search-open-panel-url-hash="#open-saved-search-panel">
<div class="inner-wrap">
<h2 class="action-panel-heading">
Your saved search
</h2>
<form id="saved-search-action-panel-form"
class="saved-search-action-panel-form action-panel-content action-form"
data-create-saved-search-url="/create-saved-search/"
data-try-search-terms-url="/try-search-term/"
data-saved-search-root-url="https://www.ncbi.nlm.nih.gov/myncbi/searches/">
<input type="hidden" name="csrfmiddlewaretoken" value="CJRrPPqtWM7A6xorlcWQFix5Wz5P6chdTwBwsFTPwnU40YuhYvzS9q3JuDN1ZNPx">
<div class="action-panel-control-wrap">
<label for="saved-search-name" class="action-panel-label saved-search-name-label required-field-asterisk">
Name of saved search:
</label>
<input maxlength="200"
type="text"
name="saved-search-name"
id="saved-search-name"
class="saved-search-name"
value=""
required
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/">
</div>
<div class="action-panel-control-wrap">
<label for="saved-search-term" class="action-panel-label required-field-asterisk">
Search terms:
</label>
<textarea name="saved-search-term" id="saved-search-term" class="saved-search-term" required></textarea>
</div>
<div class="test-search-term-wrap">
<a href="#" class="try-search-term">Test search terms</a>
</div>
<div class="choice-group action-panel-extra-margin-top">
<span class="action-panel-label" id="fieldset-label">
Would you like email updates of new search results?
</span>
<fieldset id="saved-search-alert" aria-describedby="fieldset-label">
<legend class="usa-sr-only">Saved Search Alert Radio Buttons</legend>
<ul class="radio-group-items">
<li>
<input type="radio" id="saved-search-alert-yes" class="saved-search-alert-yes" name="saved-search-alert" value="yes" checked>
<label for="saved-search-alert-yes" class="action-panel-label">Yes</label>
</li>
<li>
<input aria-label="No radio input" type="radio" id="saved-search-alert-no" class="saved-search-alert-no" name="saved-search-alert" value="no">
<label for="saved-search-alert-no" class="action-panel-label">No</label>
</li>
</ul>
</fieldset>
</div>
<div class="alert-schedule-wrap">
<div class="action-panel-control-wrap">
<label class="action-panel-label">
Email:
</label>
<span aria-label="Email address" id="saved-search-email" class="action-panel-label"><span class="action-panel-label-bold"></span> (<a class="myncbi-account-settings" href="https://www.ncbi.nlm.nih.gov/account/settings/">change</a>)</span>
</div>
<div class="action-panel-control-wrap action-panel-extra-margin-top">
<label for="saved-search-frequency" class="action-panel-label">
Frequency:
</label>
<select id="saved-search-frequency" class="no-border-panel-selector saved-search-frequency">
<option value="monthly">Monthly</option>
<option value="weekly">Weekly</option>
<option value="daily">Daily</option>
</select>
</div>
<div class="action-panel-control-wrap saved-search-monthly-additional">
<label for="saved-search-monthly-on-day" class="action-panel-label">
Which day?
</label>
<select id="saved-search-monthly-on-day" class="no-border-panel-selector">
<option value="Sunday">The first Sunday</option>
<option value="Monday">The first Monday</option>
<option value="Tuesday">The first Tuesday</option>
<option value="Wednesday">The first Wednesday</option>
<option value="Thursday">The first Thursday</option>
<option value="Friday">The first Friday</option>
<option value="Saturday">The first Saturday</option>
<option value="day">The first day</option>
<option value="weekday">The first weekday</option>
</select>
</div>
<div class="action-panel-control-wrap saved-search-weekly-additional">
<label for="saved-search-weekly-on-day" class="action-panel-label">
Which day?
</label>
<select id="saved-search-weekly-on-day" class="no-border-panel-selector saved-search-weekly-on-day">
<option value="Sunday">Sunday</option>
<option value="Monday">Monday</option>
<option value="Tuesday">Tuesday</option>
<option value="Wednesday">Wednesday</option>
<option value="Thursday">Thursday</option>
<option value="Friday">Friday</option>
<option value="Saturday">Saturday</option>
</select>
</div>
<div class="action-panel-control-wrap">
<label for="saved-search-report" class="action-panel-label">
Report format:
</label>
<select id="saved-search-report" class="no-border-panel-selector saved-search-report">
<option value="DocSum">Summary</option>
<option value="DocSumText">Summary (text)</option>
<option value="Abstract">Abstract</option>
<option value="AbstractText">Abstract (text)</option>
<option value="MEDLINE">PubMed</option>
</select>
</div>
<div class="action-panel-control-wrap">
<label for="saved-search-amount" class="action-panel-label">
Send at most:
</label>
<select id="saved-search-amount" class="no-border-panel-selector saved-search-amount">
<option value="1">1 item</option>
<option value="5" selected>5 items</option>
<option value="10">10 items</option>
<option value="20">20 items</option>
<option value="50">50 items</option>
<option value="100">100 items</option>
<option value="200">200 items</option>
</select>
</div>
<div>
<input type="checkbox" id="saved-search-send-if-no-result" class="saved-search-send-if-no-result" name="saved-search-send-if-no-result">
<label for="saved-search-send-if-no-result" class="action-panel-label smaller-checkbox">
Send even when there aren't any new results
</label>
</div>
<div class="action-panel-control-wrap option-text-in-email-wrap">
<label for="saved-search-email-text" class="action-panel-label">
Optional text in email:
</label>
<textarea name="saved-search-email-text"
id="saved-search-email-text"
class="saved-search-email-text"></textarea>
</div>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Saving..."
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="save">
Save
</button>
<button class="action-panel-cancel"
aria-label="Close 'Your saved search' panel"
ref="linksrc=close_saved_search_panel"
aria-controls="saved-search-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="citation-manager-action-panel" class="citation-manager-action-panel action-panel" aria-hidden="true">
<div class="inner-wrap">
<h2 class="action-panel-heading">
Create a file for external citation management software
</h2>
<form id="citation-manager-action-panel-form"
class="action-panel-content action-form"
action="/results-export-ids/"
data-by-search-action="/results-export-search-data/"
data-by-ids-action="/results-export-ids/"
method="post"
data-by-search-method="post"
data-by-ids-method="post">
<input type="hidden" name="csrfmiddlewaretoken" value="CJRrPPqtWM7A6xorlcWQFix5Wz5P6chdTwBwsFTPwnU40YuhYvzS9q3JuDN1ZNPx">
<input name="results-format" type="hidden" value="pubmed"/>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Sending..."
data-ga-category="save_share"
data-ga-action="citation_manager"
data-ga-label="save">
Create file
</button>
<button class="action-panel-cancel"
aria-label="Close 'Send citations to citation manager' panel"
ref="linksrc=close_citation_manager_panel"
aria-controls="citation-manager-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="citation_manager"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="rss-action-panel" class="rss-action-panel action-panel " aria-hidden="true">
<div class="inner-wrap">
<h2 class="action-panel-heading">
Your RSS Feed
</h2>
<form id="rss-action-panel-form"
class="rss-action-panel-form action-panel-content action-form"
data-create-rss-feed-url="/create-rss-feed-url/"
data-search-form-term-value="">
<input type="hidden" name="csrfmiddlewaretoken" value="CJRrPPqtWM7A6xorlcWQFix5Wz5P6chdTwBwsFTPwnU40YuhYvzS9q3JuDN1ZNPx">
<div class="action-panel-control-wrap">
<label for="rss-name" class="action-panel-label required-field-asterisk">
Name of RSS Feed:
</label>
<input maxlength="200"
placeholder="Name"
type="text"
name="rss-name"
id="rss-name"
class="rss-name"
value=''
required
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/">
</div>
<div class="rss-limit-wrap">
<div class="action-panel-control-wrap action-panel-extra-margin-top">
<label for="rss-limit" class="action-panel-label">
Number of items displayed:
</label>
<select id="rss-limit" class="no-border-panel-selector rss-limit">
<option value="5">5</option>
<option value="10">10</option>
<option value="15" selected="selected">15</option>
<option value="20">20</option>
<option value="50">50</option>
<option value="100">100</option>
</select>
</div>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Creating..."
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="save">
Create RSS
</button>
<button class="action-panel-cancel"
aria-label="Close 'Your RSS' panel"
ref="linksrc=close_rss_panel"
aria-controls="rss-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="cancel">
Cancel
</button>
</div>
<div class="action-panel-control-wrap rss-link-copy-wrap">
<label for="rss-link" class="usa-sr-only">RSS Link</label>
<input placeholder="Your RSS Feed Link" type="text" name="rss-link" id="rss-link" class="rss-link" title="RSS Link">
<button
type="button"
disabled
class="rss-link-copy-button disabled"
data-ga-category="save_share"
data-ga-action="rss"
data-ga-label="copy">
Copy
</button>
</div>
</form>
</div>
</div>
</div>
</div>
<div class="article-page" id="article-page" data-article-pmid="25370693">
<aside class="page-sidebar">
<div class="inner-wrap">
<div class="full-text-links">
<div class="full-view">
<h3 class="title">
Full text links
</h3>
<div class="full-text-links-list">
<a class="link-item
dialog-focus"
href="https://doi.org/10.1038/nrm3902"
target="_blank"
rel="noopener"
ref="linksrc=fulltextorjournal_fulltext&amp;is_pmc=False&amp;PrId=3094&amp;itool=Abstract-def&amp;log$=linkouticon&amp;uid=25370693&amp;db=pubmed&amp;nlmid=100962782"
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data-ga-category="full_text"
data-ga-action="Nature Publishing Group"
data-ga-label="25370693"
><img src="https://cdn.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--www.nature.com-static-images-logos-nature-portfolio-120.png" alt="Nature Publishing Group full text link"><span class="text">
Nature Publishing Group
</span></a><a class="link-item
pmc
"
href="https://pmc.ncbi.nlm.nih.gov/articles/pmid/25370693/"
target="_blank"
rel="noopener"
ref="linksrc=fulltextorjournal_fulltext&amp;is_pmc=True&amp;PrId=3494&amp;itool=Abstract-def&amp;log$=linkouticon&amp;uid=25370693&amp;db=pubmed&amp;nlmid=100962782"
title="Free full text at PubMed Central"
data-ga-category="full_text"
data-ga-action="PMC"
data-ga-label="25370693"
><span class="text">
Free PMC article
</span></a>
</div>
</div>
<div class="short-view">
<a href="#" class="full-text-links-button full-text-links-dialog-trigger">
Full text links
</a>
</div>
</div>
<div class="actions-buttons sidebar"><h3 class="title">Actions</h3><div class="inner-wrap"><button class="citation-button citation-dialog-trigger"
aria-label="Open dialog with citation text in different styles"
data-ga-category="save_share"
data-ga-action="cite"
data-ga-label="open"
data-all-citations-url="/25370693/citations/"
data-citation-style="nlm"
data-pubmed-format-link="/25370693/export/"><span class="button-label">Cite</span></button><link type="text/css" href="ncbi-overlay-block/src/overlay-block.css"><div class="collections-button-container" data-article-id="25370693" data-article-db="pubmed"><button class="collections-button collections-dialog-trigger"
aria-label="Save article in MyNCBI collections."
data-ga-category="collections_button"
data-ga-action="click"
data-ga-label="collections_button"
data-collections-open-dialog-enabled="false"
data-collections-open-dialog-url="https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F25370693%2F%23open-collections-dialog"
data-in-collections="false"><span class="button-label">Collections</span></button><div class="overlay" role="dialog"><div id="collections-action-dialog"
class="dialog collections-dialog"
aria-hidden="true"><div class="title">Add to Collections</div><div class="collections-action-panel action-panel"><form id="collections-action-dialog-form"
class="collections-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
data-existing-collections-url="/list-existing-collections/"
data-add-to-existing-collection-url="/add-to-existing-collection/"
data-create-and-add-to-new-collection-url="/create-and-add-to-new-collection/"
data-myncbi-max-collection-name-length="100"
data-collections-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/"><input type="hidden" name="csrfmiddlewaretoken" value="CJRrPPqtWM7A6xorlcWQFix5Wz5P6chdTwBwsFTPwnU40YuhYvzS9q3JuDN1ZNPx"><div class="choice-group" role="radiogroup"><ul class="radio-group-items"><li><input type="radio"
id="collections-action-dialog-new"
class="collections-new"
name="collections"
value="new"
data-ga-category="collections_button"
data-ga-action="click"
data-ga-label="collections_radio_new"><label for="collections-action-dialog-new">Create a new collection</label></li><li><input type="radio"
id="collections-action-dialog-existing"
class="collections-existing"
name="collections"
value="existing"
checked="true"
data-ga-category="collections_button"
data-ga-action="click"
data-ga-label="collections_radio_existing"><label for="collections-action-dialog-existing">Add to an existing collection</label></li></ul></div><div class="controls-wrapper"><div class="action-panel-control-wrap new-collections-controls"><label for="collections-action-dialog-add-to-new" class="action-panel-label required-field-asterisk">
Name your collection:
</label><input
type="text"
name="add-to-new-collection"
id="collections-action-dialog-add-to-new"
class="collections-action-add-to-new"
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/"
maxlength="100"
data-ga-category="collections_button"
data-ga-action="create_collection"
data-ga-label="non_favorties_collection"><div class="collections-new-name-too-long usa-input-error-message selection-validation-message">
Name must be less than 100 characters
</div></div><div class="action-panel-control-wrap existing-collections-controls"><label for="collections-action-dialog-add-to-existing" class="action-panel-label">
Choose a collection:
</label><select id="collections-action-dialog-add-to-existing"
class="action-panel-selector collections-action-add-to-existing"
data-ga-category="collections_button"
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The biochemical and biophysical properties of the extracellular matrix (ECM) dictate tissue-specific cell behaviour. The molecules that are associated with the ECM of each tissue, including collagens, proteoglycans, laminins and fibronectin, and the manner in which they are assembled determine the structure and the organization of the resultant ECM. The product is a specific ECM signature that is comprised of unique compositional and topographical features that both reflect and facilitate the functional requirements of the tissue.
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<p xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:p1="http://pubmed.gov/pub-one">The authors declare no competing interests.</p>
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<p> Figure 1. Collagen structure </p>
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<div class="figure-caption-contents"><b> a </b> | The…</div>
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<p> Figure 1. Collagen structure </p>
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<div class="figure-caption-contents"><b> a </b> | The standard fibrillar collagen molecule is characterized by amino-…</div>
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Figure 1. Collagen structure
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<div class="figure-caption-contents"><b>a</b> | The standard fibrillar collagen molecule is characterized by amino- and carboxy-terminal propeptide sequences, which flank a series of Gly-X-Y repeats (where X and Y represent any amino acids but are frequently proline and hydroxyproline) (step 1). These form the central triple helical structure of procollagen and collagen. Three α-chains (the illustration shows two α1-chains and one α2-chain, which is representative of type I collagen) are intracellularly assembled into the triple helix following initiation of this process by the C-terminal domain (step 2). Procollagen is secreted by cells into the extracellular space (step 3) and converted into collagen by the removal of the N- and C-propeptides via metalloproteinase enzymes (step 4). <b>b</b> | Fibril-associated collagens with interrupted triple helices (FACIT) and related collagens have a different structure to standard fibrillar collagen; they contain non-collagenous regions — that is, non-triple helical sequences. These lead to kinks in the resulting macromolecular structure that straighten under small strains. Figure part <b>a</b> is modified, with permission, from REF © 2012 Fan <i>et al</i>.; licensee BioMed Central Ltd, and from REF. , Klug, William S.; Cummings, Michael R., Concepts of Genetics, 5th Edition, © 1997. Reprinted by permission of Pearson Education, Inc., Upper Saddle River, NJ. Figure part <b>b</b>: this figure was originally published in <i>Biochem. J</i>. Jäälinoja, J., Ylöstalo, J., Beckett, W., Hulmes, D. J. S. &amp; Ala-Kokko, L., Trimerization of collagen IX alpha-chains does not require the presence of the COL1 and NC1 domains. <i>Biochem. J</i>. 2008; <b>409</b>: 545554 © the Biochemical Society.</div>
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<p> Figure 2. Fibrillar collagen assembly </p>
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<div class="figure-caption-contents"><b> a </b> |…</div>
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<p> Figure 2. Fibrillar collagen assembly </p>
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<div class="figure-caption-contents"><b> a </b> | After procollagen is secreted into the extracellular space,…</div>
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Figure 2. Fibrillar collagen assembly
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<div class="figure-caption-contents"><b>a</b> | After procollagen is secreted into the extracellular space, collagen type-specific metalloproteinase enzymes remove the amino- and carboxy-propeptides. Collagen is assembled into cross-striated microfibrils that occur in the extracellular matrix of connective tissues. This can be observed via electron microscopy as regularly spaced bands, as represented by the grey, striped bar. The position of non-fibrillar collagens in this structure is shown in similar diagrams in part b. Short microfibrils merge into mature fibrils through longitudinal and axial growth. To form mature fibres, lysyl oxidase catalyses the formation of intramolecular and intermolecular covalent crosslinks between collagen molecules. Fibres are bundled together within a connective tissue and stabilized via interactions with fibril-associated collagens with interrupted triple helices (FACIT) collagens and small leucine-rich repeat proteoglycans (SLRPs) into linear structures capable of transmitting tensile forces. Specifically in the case of tendons, fibres ranging in size from 1 μm to 20 μm are bundled into 15 400 μm diameter triangular subfascicles, subfascicles are bundled into 150 1000 μm fascicles and fascicles are grouped into tertiary bundles ranging from 1000 μm to 3000 μm. Finally, multiple tertiary bundles are enclosed by the epitenon connective tissue, which contains the vascular, lymphatic and nerve sources for the tendon tissue. <b>b</b> | In addition to fibrillar collagen, other collagen subtypes, such as type V and FACIT collagens, are incorporated into the fibril structure. Type V collagen is inserted between strands of the microfibril, and FACIT collagens cling to the surface of the microfibril and work with SLRPs to stabilize higher order structures. Figure part <b>a</b> is modified, with permission, from REF. © 2012 Fan <i>et al</i>.; licensee BioMed Central Ltd, from Klug, William S.; Cummings, Michael R., Concepts of Genetics, 5th Edition, © 1997 (REF. 136). Reprinted by permission of Pearson Education, Inc., Upper Saddle River, NJ, and from REF. , reprinted from <i>Trends Biotechnol.</i>, <b>26</b>, Liu, Y., Ramanath, H. S. &amp; Wang, D.-A., Tendon tissue engineering using scaffold enhancing strategies, 201209, Copyright (2008), with permission from Elsevier. Figure part <b>b</b>: this figure was originally published in <i>Biochem. J</i>. Jäälinoja, J., Ylöstalo, J., Beckett, W., Hulmes, D. J. S. &amp; Ala-Kokko, L., Trimerization of collagen IX alpha-chains does not require the presence of the COL1 and NC1 domains. <i>Biochem. J</i>. 2008; <b>409</b>: 545554 © the Biochemical Society.</div>
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<p> Figure 3. Non-collagenous molecules of the ECM </p>
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<p> Figure 3. Non-collagenous molecules of the ECM </p>
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<div class="figure-caption-contents"><p> Lecticans (aggrecan is shown; part <b> a </b> ) and… </p></div>
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Figure 3. Non-collagenous molecules of the ECM
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<div class="figure-caption-contents">Lecticans (aggrecan is shown; part <b>a</b>) and small leucine-rich repeat proteoglycans (SLRPs; decorin, biglycan and lumican are shown; part <b>b</b>) are major proteoglycans (PGs). The SLRPs are characterized by differences in their amino terminus structure and highly conserved leucine rich repeats (LRR) in the core molecule. Lecticans have a core protein with binding domains for glycosaminoglycan (GAG) chains flanked by globular domains that interact with hyaluronic acid (at the N terminus) and tenascin R (at the carboxy terminus). Common GAGs include chondroitin sulphate and heparan sulphate, the chemical structures of which are depicted. The assembled bottle-brush-like aggrecan link protein hyaluronic acid structure is shown. Laminins are formed by the incorporation of α, β and γ chains into a cruciform, Y-shaped or rod-like structure (part <b>c</b>). These chains are characterized by different domains, as shown. The domain structures depicted represent only one isoform for each chain type, but major differences between the basic composition of the chains (such as the lack of globular regions in β and γ chains) are also present in the other isoforms. Laminins interact with cell surface receptors, such as integrins, primarily through globular domains in the chain. Fibronectin domain structure and the domains to which extracellular matrix (ECM) molecules and cell surface receptors bind are indicated (part <b>d</b>). The fibronectin molecule forms a dimer through disulphide bonds on its C terminus. The folded fibronectin molecule forms via ionic interactions between type III domains of neighbouring molecules and is deformed by mechanical force to reveal cryptic binding sites for other fibronectin molecules and cell surface receptors when interacting with cells. Figure part <b>a</b>: this image originally appeared in Diamond Light Source Ltds Annual Report 2010 (p7273) and has been reproduced with permission from Diamond Light Source Ltd, the University of Liverpool, T. R. Rudd, M. A. Skidmore, S. E. Guimond, R. Xu, R. Hussain, D. G. Fernig, G. Siligardi and E. A. Yates <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://www.diamond.ac.uk/Science/Research/Highlights/study2.html">http://www.diamond.ac.uk/Science/Research/Highlights/study2.html</ext-link>. Figure part <b>b</b> is modified from REF. , Nature Publishing Group. Figure part <b>c</b> is modified, with permission, from Yurchenco, P. D. Basement membranes: cell scaffoldings and signaling platforms. <i>Cold Spring Harb. Perspect. Biol.</i>
<b>3</b>, a004911 (2011), Cold Spring Harbour Laboratory Press, and REF. , Nature Publishing Group. Figure part <b>d</b> is modified, with permission, from Schwarzbauer, J. E. &amp; DeSimone, D. W. Fibronectins, their fibrillogenesis, and <i>in vivo</i> functions. <i>Cold Spring Harb. Perspect. Biol.</i>
<b>3</b>, a005041 (2011), Cold Spring Harbour Laboratory Press, and REF. , modified with permission from <i>Annual Review of Cell Dev. Biol.</i>, Volume <b>26</b> by Annual Reviews, <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://www.annualreviews.org">http://www.annualreviews.org</ext-link>. EGF, epidermal growth factor; LM domain, laminin domain.</div>
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<p> Figure 4. Basal lamina assembly </p>
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<div class="figure-caption-contents"><p> Two major… </p></div>
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<p> Figure 4. Basal lamina assembly </p>
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<div class="figure-caption-contents"><p> Two major collagens participate in the assembly of the basal… </p></div>
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Figure 4. Basal lamina assembly
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<div class="figure-caption-contents">Two major collagens participate in the assembly of the basal lamina: collagen IV and collagen VII. <b>a</b> | Collagen IV is characterized by an amino-terminal 7S domain and a carboxy-terminal NC1 domain these are globular domains that facilitate the formation of hexamers and dimers, respectively. These then form highly ordered lattice structures, as shown. <b>b</b> | Collagen VII forms long dimers that then bend and connect with the globular regions of collagen IV lattices. <b>c</b> | Components of the basal lamina, and how they interact, are shown on the left-hand side. Within the basal lamina, laminins form a sheet on the cell surface by recruiting soluble laminin. This sheet is reinforced via interactions among chains of different laminin molecules and by binding between laminin globular regions and cell surface receptors (for example, integrins and dystroglycan). Collagen IV binds to laminins via nidogens and forms a scaffold on top of the laminins. This scaffold is further secured by collagen VII, which, in its unbent form (sometimes termed anchoring fibrils), can link the basal lamina to the reticular lamina to form the basement membrane. Assembled basal lamina is shown on the right-hand side. Figure parts <b>a</b> and <b>b</b> are modified from REF. , Nature Publishing Group. Figure part <b>c</b> is modified from REF. , Nature Publishing Group, with permission, from Yurchenco, P. D. Basement membranes: cell scaffoldings and signaling platforms. <i>Cold Spring Harb. Perspect. Biol.</i>
<b>3</b>, a004911 (2011), Cold Spring Harbor Laboratory Press and from REF. , Nature Publishing Group. DG, dystroglycan.</div>
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<p> Figure 5. Perineuronal nets </p>
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<div class="figure-caption-contents"><p> Perineuronal nets (PNNs)… </p></div>
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<p> Figure 5. Perineuronal nets </p>
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<div class="figure-caption-contents"><p> Perineuronal nets (PNNs) surround cells of the brain and act as… </p></div>
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Figure 5. Perineuronal nets
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<div class="figure-caption-contents">Perineuronal nets (PNNs) surround cells of the brain and act as inhibitors of both growth and migration. PNNs are lattices of hyaluronic acid, proteoglycans and tenascin molecules. The basic structure of a PNN is depicted here. Hyaluronic acid chains coated with proteoglycans are linked by trimeric tenascin R molecules to form a fairly organized structure around neurons. The chondroitin sulphate proteoglycans (CSPGs) within the net bind to cell surface CSPGs and can thus control cell behaviour. Figure modified from REF. , Nature Publishing Group.</div>
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