November 26, 2024
Publications
>
Article

Cell response to extracellular matrix viscous energy dissipation outweighs high-rigidity sensing

Publicated to: Science Advances. 10 (46): eadf9758- - 2024-11-15 10(46), DOI: 10.1126/sciadv.adf9758

Authors:

Huerta-López, C; Clemente-Manteca, A; Vellázquez-Carreras, D; Espinosa, FM; Sanchez, JG; Martínez-del-Pozo, A; García-García, M; Martín-Colomo, S; Rodríguez-Blanco, A; Esteban-González, R; Martín-Zamora, FM; Gutierrez-Rus, LI; Garcia, R; Roca-Cusachs, P; Elosegui-Artola, A; del Pozo, MA; Herrero-Galán, E; Sáez, P; Plaza, GR; Alegre-Cebollada, J
[+]

Affiliations

Barcelona Inst Sci & Technol BIST, Inst Bioengn Catalonia IBEC, Barcelona, Spain - Author
CSIC, Inst Ciencia Mat Madrid, Madrid 28049, Spain - Author
Ctr Nacl Invest Cardiovasc CNIC, Madrid 28029, Spain - Author
Francis Crick Inst, Cell & Tissue Mechanobiol Lab, 1 Midland Rd, London NW1 1AT, England - Author
Inst Matematiques UPC BarcelonaTech IMTech, Barcelona, Spain - Author
Kings Coll London, Dept Phys, London WC2R, England - Author
Univ Barcelona, Barcelona, Spain - Author
Univ Complutense Madrid, Fac CC Quim, Dept Bioquim & Biol Mol, Madrid 28040, Spain - Author
Univ Politecn Catalunya BarcelonaTech, Lab Calcul Numer LaCaN, Barcelona, Spain - Author
Univ Politecn Madrid, ETSI Caminos & Ctr Biomed Technol, Madrid 28040, Spain - Author
See more

Abstract

The mechanics of the extracellular matrix (ECM) determine cell activity and fate through mechanoresponsive proteins including Yes-associated protein 1 (YAP). Rigidity and viscous relaxation have emerged as the main mechanical properties of the ECM steering cell behavior. However, how cells integrate coexisting ECM rigidity and viscosity cues remains poorly understood, particularly in the high-stiffness regime. Here, we have exploited engineered stiff viscoelastic protein hydrogels to show that, contrary to current models of cell-ECM interaction, substrate viscous energy dissipation attenuates mechanosensing even when cells are exposed to higher effective rigidity. This unexpected behavior is however readily captured by a pull-and-hold model of molecular clutch-based cell mechanosensing, which also recapitulates opposite cellular response at low rigidities. Consistent with predictions of the pull-and-hold model, we find that myosin inhibition can boost mechanosensing on cells cultured on dissipative matrices. Together, our work provides general mechanistic understanding on how cells respond to the viscoelastic properties of the ECM.
[+]

Keywords

AdhesionAnimalsDefinesDynamicsElasticityExtracellular matrixForceHumansHydrogelsMechanotransductionMechanotransduction, cellularStabilityTaliViscosityYap/taz

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Science Advances due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2024 there are still no calculated indicators, but in 2023, it was in position 12/136, thus managing to position itself as a Q1 (Primer Cuartil), in the category Multidisciplinary Sciences. Notably, the journal is positioned above the 90th percentile.

Independientemente del impacto esperado determinado por el canal de difusión, es importante destacar el impacto real observado de la propia aportación.

Según las diferentes agencias de indexación, el número de citas acumuladas por esta publicación hasta la fecha 2026-04-11:

  • Google Scholar: 5
  • WoS: 18
  • Scopus: 18
[+]

Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2026-04-11:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 58.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 58 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 65.
  • The number of mentions on the social network X (formerly Twitter): 37 (Altmetric).
  • The number of mentions in news outlets: 4 (Altmetric).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.
  • Assignment of a Handle/URN as an identifier within the deposit in the Institutional Repository: https://oa.upm.es/86823/

As a result of the publication of the work in the institutional repository, statistical usage data has been obtained that reflects its impact. In terms of dissemination, we can state that, as of

  • Views: 172
  • Downloads: 32
[+]

Leadership analysis of institutional authors

This work has been carried out with international collaboration, specifically with researchers from: United Kingdom.

[+]

Awards linked to the item

J.A.-C. acknowledges funding from the Ministerio de Ciencia, Innovacion y Universidades (MCIU, MICIU/AEI/10.13039/501100011033) through grants BIO2014- 54768- P, BIO2017-83640-P (AEI/FEDER, UE), and RYC- 2014- 16604 and from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (grant agreement no. 101002927). Research in R.E.-G. laboratory was funded by MCIU grant PID2022- 136851NB-I00. A.M.-P. acknowledges funding from Universidad Complutense-Banco Santander Grants PR87/19-22556 and PR108/20- 26896. M.A.P. lab was supported by PID2020- 118658RB-I00 and PDC2021- 121572- 100 (MCIU) and by Fundacio La Marato deTV3 (201936- 30- 31). R.E.-G., M.A.P., G.R.P., and J.A.-C. laboratories are supported by a collaborative grant from the Comunidad de Madrid (consortium Tec4Bio-CM, S2018/NMT-4443, 50% cofinanced by the European Social Fund and the European Regional Development Fund for the programming period 2014- 2020). R.E.-G., P.R.-C., M.A.P., and J.A.-C. are members of the Spanish Network of Excellence in Mechanobiology (RED2022- 134242- T funded by MCIU). A.E.-A. received funding from ERC under the European Union's Horizon 2020 research and innovation programme (grant agreement no.851055). A.E.-A. is supported by the Francis Crick Institute, which receives its core funding from Cancer Research UK (CC2214), the UK Medical Research Council (CC2214), and the WellcomeTrust (CC2214). P.S. acknowledges support from MCIU (grant no. PID2019- 110949GB-I00), the European Commission (grant no. H2020- FETPROACT-01- 2016- 731957), and the Generalitat de Catalunya (grant no. 2021-SGR-01049). P.R.-C. acknowledges funding from MCIU (PID2019- 110298GB-I00), the European Commission (H2020-FETPROACT-01-2016-731957), the Generalitat de Catalunya (2017-SGR-1602), the prize "ICREA Academia"for excellence in research, and "la Caixa" Foundation (agreement LCF/PR/HR20/52400004). IBEC is a recipient ofa Severo Ochoa Award of Excellence from MCIU. CNIC is supported by the Instituto de Salud Carlos III (ISCIII), MCIU, and the Pro CNIC Foundation and is a Severo Ochoa Center of Excellence (grant CEX2020- 001041- S funded by MCIU). C.H.-L. was the recipient of an FPI predoctoral fellowship BES- 2015- 073191. M.G.-G. was sponsored by an FPU fellowship (FPU15/03776). A.C.-M. was the recipient of a Master CNIC ACCIONA fellowship (2022 Call, #632065).
[+]