Deciphering the role of intra and extracellular elasticity for protrusion growth, stability and switching during cell motility in vivo.
Developmental Biology
Cell Biology
Final Report Abstract
Elastic properties of the cell environment, for example in tissues, have emerged as a key parameter that regulate not only migration, but also cell differentiation. During the funding period we have advanced our understanding of the role of tissue and extracellular matrix elasticity in key biological questions and pushed the development and use of Brillouin microscopes to measure mechanical properties of biosamples in a non-destructive, label- and contact-free way. Specifically, we have advanced our understanding of the role of tissue elasticity for cancer progression. Combining patient samples from the clinic with our atomic force microscopy (AFM) measurements of tissue stiffness we could show that renin-angiotensin inhibitors act on metastasisassociated fibroblasts to reduce tissue stiffness and increase the efficacy of anti-angiogenic therapy. In fact, metastatic colorectal cancer patients treated with the gold standard anti-angiogenic drug (bevacizumab) showed prolonged survival when concomitantly treated with renin-angiotensin inhibitors, which are used to control blood pressure. Moreover, during the funding period we have established ourselves as pioneers in the BioBrillouin field. In close collaboration with the Prevedel lab, we have implemented and characterized a confocal Brillouin microscope. Viscoelastic properties are deduced from the light scattering of thermally induced acoustic modes or phonons in the GHz frequency range with submicrometer spatial resolution. We have used this microscope to quantify tissue mechanics during notochord and eye development in zebrafish embryos. Moreover, we have employed it to study the role of extracellular elasticity during cell migration in vitro and in vivo, in collaboration with the Vignjevic lab, at the Curie Institute in Paris, and the Raz lab, at the University of Muenster, respectively. Last, we are currently working towards deciphering the molecular origin of the Brillouin shift and contributed to the development of the first line-scan Brillouin microscope. Such work will open the door to understanding the mechanical meaning of a Brillouin map and generate stiffness maps with a higher throughput and coverage.
Publications
- (2019). Brillouin microscopy: an emerging tool for mechanobiology. Nat. Methods 16(10):969-977
Prevedel R, Diz-Muñoz A, Ruocco G, Antonacci G
(See online at https://doi.org/10.1038/s41592-019-0543-3) - (2019). Imaging mechanical properties of sub-micron ECM in live zebrafish using Brillouin microscopy. Biomed Opt Express. 10(3):1420-1431
Bevilacqua C, Sánchez-Iranzo H, Richter D, Diz-Muñoz A, Prevedel R
(See online at https://doi.org/10.1364/boe.10.001420) - (2020). A 3D Brillouin microscopy dataset of the in-vivo zebrafish eye. Data Brief. 30
Sánchez-Iranzo H, Bevilacqua C, Diz-Muñoz A, Prevedel R
(See online at https://doi.org/10.1016/j.dib.2020.105427) - (2020). Protocol on tissue preparation and measurement of tumor stiffness in primary and metastatic colorectal cancer samples with an atomic force microscope. STAR Protoc. 1(3)
Shen Y, Schmidt T, Diz-Muñoz A
(See online at https://doi.org/10.1016/j.xpro.2020.100167) - (2020). Reduction of liver metastasis stiffness improves response to bevacizumab in metastatic colorectal cancer. Cancer Cell. 37(6):800-817.e7
Shen Y, Wang X, Lu J, Salfenmoser M, Wirsik NM, Schleussner N, Imle A, Freire Valls A, Radhakrishnan P, Liang J, Wang G, Muley T, Schneider M, Ruiz de Almodovar C, Diz-Muñoz A, Schmidt T
(See online at https://doi.org/10.1016/j.ccell.2020.05.005) - (2022). Viscoelastic relaxation of collagen networks provides a self-generated directional cue during collective migration. Nat. Mater.
Clark AG, Maitra A, Jacques C, Bergert M, Pérez-González C, Simon A, Lederer L, Diz-Muñoz A, Trepat X, Voituriez R, Vignjevic DM
(See online at https://doi.org/10.1101/2020.07.11.198739) - 2022. High-resolution line-scan Brillouin microscopy for live-imaging of mechanical properties during embryo development. bioRxiv
Bevilacqua C, Gomez JM, Fiuza UM, Chan CJ, Wang L, Hambura S, Eguren M, Ellenberg J, Diz-Muñoz A, Leptin M, Prevedel R
(See online at https://doi.org/10.1101/2022.04.25.489364)
