Evidence map›Paper›PMID 27941914›Full record

ArticleScientific reports2016

High fidelity visualization of cell-to-cell variation and temporal dynamics in nascent extracellular matrix formation.

Claire M McLeod, Robert L Mauck

Abstract readVideo-Audio Media
In one paragraph

Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed
–field-weighted citation impact
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

42 citing papers in PubMed.

  1. Nascent Extracellular Matrix Converts Biomaterial Cues into Cell Fate Decisions.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
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  16. Mechanoepigenetic regulation of extracellular matrix homeostasis via Yap and Taz.Proceedings of the National Academy of Sciences of the United States of America · 2023
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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

2 authors.

Claire M McLeodDepartment of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104, USA.
Robert L MauckDepartment of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104, USA.

Funding

Multidisciplinary Training in Cardiovascular BiologyT32HL007954 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI DAVIES, PETER FRANCIS · 2000 to 2019
$9.9M
Overall: Resource-based Center for Musculoskeletal Disorders Research (Overall Application)P30AR069619 · NIAMS · UNIVERSITY OF PENNSYLVANIA · PI LOUIS J SOSLOWSKY · 2016 to 2026
$9.1M
The Role of Hyaluronic Acid Receptors in Tendon HealingP30AR050950 · NIAMS · UNIVERSITY OF PENNSYLVANIA · PI PIGNOLO, ROBERT JOHN · 2006 to 2015
$6.2M
Engineering Developmental Microenvironments: Cartilage Formation and MaturationR01EB008722 · NIBIB · UNIVERSITY OF PENNSYLVANIA · PI BURDICK, JASON A, MAUCK, ROBERT L · 2009 to 2017
$3.0M
NHLBI NIH HHS T32 HL007954NIAMS NIH HHS P30 AR050950NIAMS NIH HHS P30 AR069619NIBIB NIH HHS R01 EB008722
6 · The paper itself

Abstract

Extracellular matrix dynamics are key to tissue morphogenesis, homeostasis, injury, and repair. The spatiotemporal organization of this matrix has profound biological implications, but is challenging to monitor using standard techniques. Here, we address these challenges by using noncanonical amino acid tagging to fluorescently label extracellular matrix synthesized in the presence of bio-orthogonal methionine analogs. This strategy labels matrix proteins with high resolution, without compromising their distribution or mechanical function. We demonstrate that the organization and temporal dynamics of the proteinaceous matrix depend on the biophysical features of the microenvironment, including the biomaterial scaffold and the niche constructed by cells themselves. Pulse labeling experiments reveal that, in immature constructs, nascent matrix is highly fibrous and interdigitates with pre-existing matrix, while in more developed constructs, nascent matrix lacks fibrous organization and is retained in the immediate pericellular space. Inhibition of collagen crosslinking increases matrix synthesis, but compromises matrix organization. Finally, these data demonstrate marked cell-to-cell heterogeneity amongst both chondrocytes and mesenchymal stem cells undergoing chondrogenesis. Collectively, these results introduce fluorescent noncanonical amino acid tagging as a strategy to investigate spatiotemporal matrix organization, and demonstrate its ability to identify differences in phenotype, microenvironment, and matrix assembly at the single cell level.

Indexed as

AlanineAlkynesAnimalsCattleCellular MicroenvironmentChondrocytesChondrogenesisExtracellular MatrixExtracellular Matrix ProteinsFluorescent Antibody Technique, DirectFluorescent DyesGlycineMesenchymal Stem CellsMicroscopy, ConfocalMicroscopy, FluorescenceQuinolinium CompoundsAlanineAlexa fluor 546AlkynesazidohomoalanineExtracellular Matrix ProteinsFluorescent DyesGlycinehomopropargylglycineQuinolinium Compounds

Identifiers

PMID27941914
PMCPMC5150986

What OpenQuestion holds

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LicenceCC BY
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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.