Evidence map›Paper›PMID 33990464›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2021

A spatial model of YAP/TAZ signaling reveals how stiffness, dimensionality, and shape contribute to emergent outcomes.

Kiersten Elizabeth Scott, Stephanie I Fraley, Padmini Rangamani

Open access · greenAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 118 papers.

0numbers the graph read from it
0cells of the map it votes in
118citing papers in PubMed
11.3field-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

118 citing papers in PubMed, 179 citations in OpenAlex.

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  19. Evidence for Drop-Like Nuclear Deformation in Sheared Endothelial Monolayers.Small (Weinheim an der Bergstrasse, Germany) · 2026
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58 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

3 authors at 1 institution in 1 country.

Kiersten Elizabeth ScottBioengineering, Jacobs School of Engineering, University of California San Diego, La Jolla, CA 92093.ORCID 0000-0003-2970-950X
Stephanie I FraleyBioengineering, Jacobs School of Engineering, University of California San Diego, La Jolla, CA 92093; sifraley@ucsd.edu padmini.rangamani@eng.ucsd.edu.ORCID 0000-0003-1548-4442
Padmini RangamaniMechanical and Aerospace Engineering, Jacobs School of Engineering, University of California San Diego, La Jolla, CA 92093 sifraley@ucsd.edu padmini.rangamani@eng.ucsd.edu.ORCID 0000-0001-5953-4347
University of California San Diego · US

Funding

Mechanistic Modeling of Cellular SystemsR24GM137787 · NIGMS · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · PI Pedro Mendes, Ion I. Moraru · 2020 to 2026
$8.9M
NIGMS NIH HHS R24 GM137787
6 · The paper itself

Abstract

YAP/TAZ is a master regulator of mechanotransduction whose functions rely on translocation from the cytoplasm to the nucleus in response to diverse physical cues. Substrate stiffness, substrate dimensionality, and cell shape are all input signals for YAP/TAZ, and through this pathway, regulate critical cellular functions and tissue homeostasis. Yet, the relative contributions of each biophysical signal and the mechanisms by which they synergistically regulate YAP/TAZ in realistic tissue microenvironments that provide multiplexed input signals remain unclear. For example, in simple two-dimensional culture, YAP/TAZ nuclear localization correlates strongly with substrate stiffness, while in three-dimensional (3D) environments, YAP/TAZ translocation can increase with stiffness, decrease with stiffness, or remain unchanged. Here, we develop a spatial model of YAP/TAZ translocation to enable quantitative analysis of the relationships between substrate stiffness, substrate dimensionality, and cell shape. Our model couples cytosolic stiffness to nuclear mechanics to replicate existing experimental trends, and extends beyond current data to predict that increasing substrate activation area through changes in culture dimensionality, while conserving cell volume, forces distinct shape changes that result in nonlinear effect on YAP/TAZ nuclear localization. Moreover, differences in substrate activation area versus total membrane area can account for counterintuitive trends in YAP/TAZ nuclear localization in 3D culture. Based on this multiscale investigation of the different system features of YAP/TAZ nuclear translocation, we predict that how a cell reads its environment is a complex information transfer function of multiple mechanical and biochemical factors. These predictions reveal a few design principles of cellular and tissue engineering for YAP/TAZ mechanotransduction.

Indexed as

AlgorithmsModels, BiologicalSignal TransductionActinsActive Transport, Cell NucleusCell NucleusCells, CulturedCell ShapeCytoplasmCytoskeletonHumansMechanical PhenomenaNuclear PoreTranscriptional Coactivator with PDZ-Binding Motif ProteinsYAP-Signaling ProteinsActinsTranscriptional Coactivator with PDZ-Binding Motif ProteinsYAP1 protein, humanYAP-Signaling Proteinscell shapedimensionalityspatial modelingstiffnessYAP/TAZ

Identifiers

PMID33990464
PMCPMC8157940
OpenAlexW3160105984

What OpenQuestion holds

Textmetadata
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.