Brillouin Spectroscopy: From Biomedical Research to New Generation Pathology Diagnosis

Riobóo, R. J. Jiménez; Gontán, Nuria; Sanderson, Daniel; Desco, Manuel; Gómez-Gaviro, Marı́a Victoria

doi:10.3390/ijms22158055

Cited by 13 publications

(12 citation statements)

References 119 publications

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“…The resultant Brillouin frequency shift can be used to calculate the elastic (longitudinal) modulus of the sample if its density and refractive index are known. BM is currently being used and developed for diverse applications in biomedical research such as ophthalmological pathologies and basic research such as mouse embryogenesis, zebrafish development and regeneration, and cell biology [ 34 , 35 , 36 ]. Recent work has indicated that for most common biological samples the Brillouin shift can be used as a proxy for the sample’s mechanical properties [ 31 , 37 ].…”

Section: Introductionmentioning

confidence: 99%

Mapping Tumor Spheroid Mechanics in Dependence of 3D Microenvironment Stiffness and Degradability by Brillouin Microscopy

Mahajan

Beck

Gregorczyk

et al. 2021

Cancers

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Altered biophysical properties of cancer cells and of their microenvironment contribute to cancer progression. While the relationship between microenvironmental stiffness and cancer cell mechanical properties and responses has been previously studied using two-dimensional (2D) systems, much less is known about it in a physiologically more relevant 3D context and in particular for multicellular systems. To investigate the influence of microenvironment stiffness on tumor spheroid mechanics, we first generated MCF-7 tumor spheroids within matrix metalloproteinase (MMP)-degradable 3D polyethylene glycol (PEG)-heparin hydrogels, where spheroids showed reduced growth in stiffer hydrogels. We then quantitatively mapped the mechanical properties of tumor spheroids in situ using Brillouin microscopy. Maps acquired for tumor spheroids grown within stiff hydrogels showed elevated Brillouin frequency shifts (hence increased longitudinal elastic moduli) with increasing hydrogel stiffness. Maps furthermore revealed spatial variations of the mechanical properties across the spheroids’ cross-sections. When hydrogel degradability was blocked, comparable Brillouin frequency shifts of the MCF-7 spheroids were found in both compliant and stiff hydrogels, along with similar levels of growth-induced compressive stress. Under low compressive stress, single cells or free multicellular aggregates showed consistently lower Brillouin frequency shifts compared to spheroids growing within hydrogels. Thus, the spheroids’ mechanical properties were modulated by matrix stiffness and degradability as well as multicellularity, and also to the associated level of compressive stress felt by tumor spheroids. Spheroids generated from a panel of invasive breast, prostate and pancreatic cancer cell lines within degradable stiff hydrogels, showed higher Brillouin frequency shifts and less cell invasion compared to those in compliant hydrogels. Taken together, our findings contribute to a better understanding of the interplay between cancer cells and microenvironment mechanics and degradability, which is relevant to better understand cancer progression.

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Section: Introductionmentioning

confidence: 99%

Mapping Tumor Spheroid Mechanics in Dependence of 3D Microenvironment Stiffness and Degradability by Brillouin Microscopy

Mahajan

Beck

Gregorczyk

et al. 2021

Cancers

View full text Add to dashboard Cite

show abstract

“…The resultant Brillouin frequency shift can be used to calculate the elastic (longitudinal) modulus of the sample, if its density and refractive index are known. BM is currently being used and developed for diverse applications in biomedical research such as ophthalmological pathologies and basic research such as mouse embryogenesis, zebrafish development and regeneration, and cell biology (34)(35)(36). Recent work has indicated that for most common biological samples the Brillouin shift can be used as a proxy for the sample's mechanical properties (31) (42).…”

Section: Introductionmentioning

confidence: 99%

Mapping tumor spheroid mechanics in dependence of 3D microenvironment stiffness and degradability by Brillouin microscopy

Mahajan¹,

Beck

Gregorczyk

et al. 2021

Preprint

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Altered biophysical properties of cancer cells and of their microenvironment contribute to cancer progression. While the relationship between microenvironmental stiffness and cancer cell mechanical properties and responses has been previously studied using two-dimensional (2D) systems, much less is known about it in a physiologically more relevant 3D context and in particular for multicellular systems. To investigate the influence of microenvironment stiffness on tumor spheroid mechanics, we first generated MCF-7 tumor spheroids within matrix metalloproteinase (MMP)- degradable 3D polyethylene glycol (PEG)-heparin hydrogels, where spheroids showed reduced growth in stiffer hydrogels. We then quantitatively mapped the mechanical properties of tumor spheroids in situ using Brillouin microscopy. Maps acquired for tumor spheroids grown within stiff hydrogels showed elevated Brillouin frequency shifts (hence increased longitudinal elastic moduli) with increasing hydrogel stiffness. Maps furthermore revealed spatial variations of the mechanical properties across the spheroids cross-sections. When hydrogel degradability was blocked, comparable Brillouin frequency shifts of the MCF-7 spheroids were found in both compliant and stiff hydrogels, along with similar levels of growth-induced compressive stress. Under low compressive stress, single cells or free multicellular aggregates showed consistently lower Brillouin frequency shifts compared to spheroids growing within hydrogels. Thus, the spheroids mechanical properties were modulated by matrix stiffness and degradability as well as multicellularity, and also to the associated level of compressive stress felt by tumor spheroids. Spheroids generated from a panel of invasive breast, prostate and pancreatic cancer cell lines within degradable stiff hydrogels, showed higher Brillouin frequency shifts and less cell invasion compared to those in compliant hydrogels. Taken together, our findings contribute to a better understanding of the interplay between cancer cells and microenvironment mechanics and degradability, which is relevant to better understand cancer progression.

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“…Brillouin light scattering deals with the interaction of the incident light with acoustic waves, spontaneously propagating in the matter thermally activated [10,13]. In the Brillouin spectra, the peaks' intensity is directly dependent on the concentration of the elastic species supporting the acoustic mode, whereas the square of its Brillouin frequency shift, ν B , is related to the elastic species hardness, expressed by the longitudinal elastic modulus M:…”

Section: Brillouin Data Analysismentioning

confidence: 99%

“…Brillouin and Raman micro-spectroscopy (BRmS) is an optical correlative method for material characterization at the microscale based on light scattering [10,11]. Specifically, Brillouin spectroscopy describes the mechanical properties by means of the interaction of light with acoustic waves, spontaneously propagating in the matter due to thermal motions [12][13][14]. On the other hand, Raman spectroscopy is a well-established vibrational technique for the chemical characterization of organic material [15].…”

Section: Introductionmentioning

confidence: 99%

Brillouin and Raman Micro-Spectroscopy: A Tool for Micro-Mechanical and Structural Characterization of Cortical and Trabecular Bone Tissues

et al. 2021

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Human bone is a specialized tissue with unique material properties, providing mechanical support and resistance to the skeleton and simultaneously assuring capability of adaptation and remodelling. Knowing the properties of such a structure down to the micro-scale is of utmost importance, not only for the design of effective biomimetic materials but also to be able to detect pathological alterations in material properties, such as micro-fractures or abnormal tissue remodelling. The Brillouin and Raman micro-spectroscopic (BRmS) approach has the potential to become a first-choice technique, as it is capable of simultaneously investigating samples’ mechanical and structural properties in a non-destructive and label-free way. Here, we perform a mapping of cortical and trabecular bone sections of a femoral epiphysis, demonstrating the capability of the technique for discovering the morpho-mechanics of cells, the extracellular matrix, and marrow constituents. Moreover, the interpretation of Brillouin and Raman spectra merged with an approach of data mining is used to compare the mechanical alterations in specimens excised from distinct anatomical areas and subjected to different sample processing. The results disclose in both cases specific alterations in the morphology and/or in the tissue chemical make-up, which strongly affects bone mechanical properties, providing a method potentially extendable to other important biomedical issues.

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Brillouin Spectroscopy: From Biomedical Research to New Generation Pathology Diagnosis

Cited by 13 publications

References 119 publications

Mapping Tumor Spheroid Mechanics in Dependence of 3D Microenvironment Stiffness and Degradability by Brillouin Microscopy

Mapping Tumor Spheroid Mechanics in Dependence of 3D Microenvironment Stiffness and Degradability by Brillouin Microscopy

Mapping tumor spheroid mechanics in dependence of 3D microenvironment stiffness and degradability by Brillouin microscopy

Brillouin and Raman Micro-Spectroscopy: A Tool for Micro-Mechanical and Structural Characterization of Cortical and Trabecular Bone Tissues

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