Measuring age-dependent viscoelasticity of organelles, cells and organisms with time-shared optical tweezer microrheology

Mostra el registre complet Registre parcial de l'ítem

  • dc.contributor.author Català Castro, Frederic
  • dc.contributor.author Ortiz Vásquez, Santiago
  • dc.contributor.author Martínez Fernández, Carmen
  • dc.contributor.author Pezzano, Fabio
  • dc.contributor.author Garcia-Cabau, Carla
  • dc.contributor.author Fernández-Campo, Martín
  • dc.contributor.author Sanfeliu-Cerdán, Neus
  • dc.contributor.author Jiménez-Delgado, Senda
  • dc.contributor.author Salvatella, Xavier
  • dc.contributor.author Ruprecht, Verena
  • dc.contributor.author Frigeri, Paolo-Antonio
  • dc.contributor.author Krieg, Michael
  • dc.date.accessioned 2025-02-25T07:33:40Z
  • dc.date.available 2025-02-25T07:33:40Z
  • dc.date.issued 2025
  • dc.description Data de publicació electònica: 02-01-2025
  • dc.description.abstract Quantifying the mechanical response of the biological milieu (such as the cell's interior) and complex fluids (such as biomolecular condensates) would enable a better understanding of cellular differentiation and aging and accelerate drug discovery. Here we present time-shared optical tweezer microrheology to determine the frequency- and age-dependent viscoelastic properties of biological materials. Our approach involves splitting a single laser beam into two near-instantaneous time-shared optical traps to carry out simultaneous force and displacement measurements and quantify the mechanical properties ranging from millipascals to kilopascals across five decades of frequency. To create a practical and robust nanorheometer, we leverage both numerical and analytical models to analyse typical deviations from the ideal behaviour and offer solutions to account for these discrepancies. We demonstrate the versatility of the technique by measuring the liquid-solid phase transitions of MEC-2 stomatin and CPEB4 biomolecular condensates, and quantify the complex viscoelastic properties of intracellular compartments of zebrafish progenitor cells. In Caenorhabditis elegans, we uncover how mutations in the nuclear envelope proteins LMN-1 lamin A, EMR-1 emerin and LEM-2 LEMD2, which cause premature aging disorders in humans, soften the cytosol of intestinal cells during organismal age. We demonstrate that time-shared optical tweezer microrheology offers the rapid phenotyping of material properties inside cells and protein blends, which can be used for biomedical and drug-screening applications.
  • dc.description.sponsorship We would like to thank the PRBB aquatics facility for animal maintenance and the C. elegans centre (CGC, supported by the National Institutes of Health, P40 OD010440) for reagents. We thank A. Farré, E. Schäffer and the NMSB and Cell and Tissue Dynamics laboratory members for discussions. We thank P. Askjaer for C. elegans strains and the Single Molecule Biophotonics laboratory at ICFO for sharing the chemicals. M.K. acknowledges financial support from the ERC (MechanoSystems, 715243), Human Frontiers Science Program (RGP021/2023), MCIN/AEI/10.13039/501100011033/FEDER ‘A way to make Europe’ (PID2021-123812OB-I00, CNS2022-135906), ‘Severo Ochoa’ program for Centres of Excellence in R&D (CEX2019-000910-S), from Fundació Privada Cellex, Fundació Mir-Puig and from Generalitat de Catalunya through the CERCA and Research program. V.R. acknowledges financial support from the Ministerio de Ciencia y Innovacion through the Plan Nacional (PID2020-117011GB-I00) and funding from the European Union’s Horizon EIC-ESMEA Pathfinder programme 101046620 and BREAKDANCE 101072123. X.S. acknowledges funding from AGAUR (2017 SGR 324), MINECO (BIO2015-70092-R and PID2019-110198RB-I00) and the European Research Council (CONCERT, contract no. 648201). C.G.-C. acknowledges a graduate fellowship from MINECO (PRE2018-084684). IRB Barcelona and ICFO are the recipient of a Severo Ochoa Award of Excellence from MINECO (Government of Spain).
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Català-Castro F, Ortiz-Vásquez S, Martínez-Fernández C, Pezzano F, Garcia-Cabau C, Fernández-Campo M, et al. Measuring age-dependent viscoelasticity of organelles, cells and organisms with time-shared optical tweezer microrheology. Nat Nanotechnol. 2025 Jan 2. DOI: 10.1038/s41565-024-01830-y
  • dc.identifier.doi http://dx.doi.org/10.1038/s41565-024-01830-y
  • dc.identifier.issn 1748-3387
  • dc.identifier.uri http://hdl.handle.net/10230/69730
  • dc.language.iso eng
  • dc.publisher Nature Research
  • dc.relation.ispartof Nat Nanotechnol. 2025 Jan 2
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/715243
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/3PE/PID2021-123812OB-I00
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/3PE/CNS2022-135906
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/CEX2019-000910-S
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PID2020-117011GB-I00
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/HE/101046620
  • dc.rights © The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by/4.0/
  • dc.subject.keyword Biological physics
  • dc.subject.keyword Biomaterials
  • dc.subject.keyword Biomedical engineering
  • dc.subject.keyword Biosensors
  • dc.subject.keyword Characterization and analytical techniques
  • dc.title Measuring age-dependent viscoelasticity of organelles, cells and organisms with time-shared optical tweezer microrheology
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion