Evidence map›Paper›PMID 26423227›Full record

ArticleScientific reports2015

Three-dimensional matrix fiber alignment modulates cell migration and MT1-MMP utility by spatially and temporally directing protrusions.

Stephanie I Fraley, Pei-Hsun Wu, Lijuan He, Yunfeng Feng, Ranjini Krisnamurthy, Gregory D Longmore, Denis Wirtz

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 138 papers.

0numbers the graph read from it
0cells of the map it votes in
138citing papers in PubMed
9.8field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

138 citing papers in PubMed, 242 citations in OpenAlex.

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78 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 1 country.

Stephanie I FraleyDepartment of Bioengineering, University of California San Diego, La Jolla, California 92093, USA.
Pei-Hsun WuDepartment of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, Maryland 21218, USA.
Lijuan HeDepartment of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, Maryland 21218, USA.
Yunfeng FengJohns Hopkins Physical Sciences-Oncology Center, The Johns Hopkins University, Baltimore, Maryland 21218, USA.
Ranjini KrisnamurthyDepartment of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, Maryland 21218, USA.
Gregory D LongmoreJohns Hopkins Physical Sciences-Oncology Center, The Johns Hopkins University, Baltimore, Maryland 21218, USA.
Denis WirtzDepartment of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, Maryland 21218, USA.
Johns Hopkins University · USUniversity of California, San Diego · US

Funding

TRANS NETWORK PROJECTSU54CA143868 · NCI · JOHNS HOPKINS UNIVERSITY · PI SEMENZA, GREGG L · 2009 to 2013
$13.7M
Single-cell phenotyping for therapeutic stratification in pancreatic cancerR01CA174388 · NCI · JOHNS HOPKINS UNIVERSITY · PI WIRTZ, DENIS · 2012 to 2016
$3.8M
NCI NIH HHS R01 CA174388NCI NIH HHS R01CA174388NCI NIH HHS U54 CA143868NCI NIH HHS U54CA143868
6 · The paper itself

Abstract

Multiple attributes of the three-dimensional (3D) extracellular matrix (ECM) have been independently implicated as regulators of cell motility, including pore size, crosslink density, structural organization, and stiffness. However, these parameters cannot be independently varied within a complex 3D ECM protein network. We present an integrated, quantitative study of these parameters across a broad range of complex matrix configurations using self-assembling 3D collagen and show how each parameter relates to the others and to cell motility. Increasing collagen density resulted in a decrease and then an increase in both pore size and fiber alignment, which both correlated significantly with cell motility but not bulk matrix stiffness within the range tested. However, using the crosslinking enzyme Transglutaminase II to alter microstructure independently of density revealed that motility is most significantly predicted by fiber alignment. Cellular protrusion rate, protrusion orientation, speed of migration, and invasion distance showed coupled biphasic responses to increasing collagen density not predicted by 2D models or by stiffness, but instead by fiber alignment. The requirement of matrix metalloproteinase (MMP) activity was also observed to depend on microstructure, and a threshold of MMP utility was identified. Our results suggest that fiber topography guides protrusions and thereby MMP activity and motility.

Indexed as

Cell MovementCell Culture TechniquesCell Line, TumorCell ShapeCulture MediaExtracellular MatrixFibrillar CollagensGTP-Binding ProteinsHumansMatrix Metalloproteinase 14Protein Glutamine gamma Glutamyltransferase 2Protein Structure, QuaternaryTransglutaminasesCulture MediaFibrillar CollagensGTP-Binding ProteinsMatrix Metalloproteinase 14MMP14 protein, humanProtein Glutamine gamma Glutamyltransferase 2Transglutaminases

Identifiers

PMID26423227
PMCPMC4589685
OpenAlexW1876890400

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.