Monitoring contractility in single cardiomyocytes and whole hearts with bio-integrated microlasers

“…In the same vein, Wispering Galery Mode Microlasers are micron-sized deformable optical microresonators able to emit laser light pulses with a frequency dependent on their geometry 154 , and thus enabling the quantification of their deformation from their emission spectrum. These reporters have been inserted into the cytoplasm of contractile cardiomyocytes and in zebrafish hearts to monitor cell and organ contractility 155 , but they remain to be used as direct force reporters.…”

Section: Inclusionsmentioning

confidence: 99%

Measuring mechanical stress in living tissues

et al. 2020

View full text Add to dashboard Cite

Living tissues are active multifunctional materials capable of generating, sensing, withstanding and responding to mechanical stress. These capabilities enable tissues to adopt complex shapes during development, to sustain those shapes during homeostasis, and to restore them during healing and regeneration. Abnormal stress is associated with a broad range of pathologies, including developmental defects, inflammatory diseases, tumor growth and metastasis. Here we review techniques that measure mechanical stress in living tissues with cellular and subcellular resolution. We begin with 2D techniques to map stress in cultured cell monolayers, which provide the highest resolution and accessibility. These techniques include 2D traction microscopy, micro-pillar arrays, monolayer stress microscopy, and monolayer stretching between flexible cantilevers. We next focus on 3D traction microscopy and the micro-bulge test, which enable mapping forces in tissues cultured in 3D. Finally, we review techniques to measure stress in vivo, including servo-null methods for measuring luminal pressure, deformable inclusions, FRET sensors, laser ablation and computational methods for force inference. Whereas these techniques remain far from becoming everyday tools in biomedical laboratories, their rapid development is fostering key advances in the way we understand the role of mechanics in morphogenesis, homeostasis and disease.

show abstract

“…In the same vein, Whispering Gallery Mode Microlasers are micron-sized deformable optical microresonators able to emit laser light pulses with a frequency dependent on their geometry [177], and thus enabling the quantification of their deformation from their emission spectrum. These reporters have been inserted into the cytoplasm of contractile cardiomyocytes and in zebrafish hearts to monitor cell and organ contractility [178], but they remain to be used as direct force reporters.…”

Section: Inclusionsmentioning

confidence: 99%

Active superelasticity in three-dimensional epithelia of controlled shape

Latorre Ibars

View full text Add to dashboard Cite

Fundamental processes in development and physiology are determined by the three-dimensional architecture of epithelial sheets. How these sheets deform and fold into complex structures has remained unclear, however, because their mechanical properties in three-dimensions have not been accessed experimentally. By combining measurements of epithelial tension, shape, and luminal pressure with mathematical modeling, here we show that epithelial cell sheets are active superelastic materials. We develop a new approach to produce massive arrays of epithelial domes with controlled basal shape and size. By measuring 3D deformations of the substrate and curvature of the dome we obtain a direct measurement of luminal pressure and epithelial tension. Observations over time-scales of hours allow us to map the epithelial tension-strain response, revealing a tensional plateau over several-fold areal strain reaching 300%. We show that these extreme nominal strains are accommodated by a highly heterogeneous stretching of individual cells, with barely deformed cells coexisting with others reaching 1000% areal strain, in seeming contradiction with the measured tensional uniformity. This phenomenology is reminiscent of superelasticity, a mechanical response generally attributed to microscopic material instabilities in metal alloys. We provide evidence that this instability is triggered in epithelial cells by a stretch-induced dilution of the actin cortex and rescued by the intermediate filament network. Finally, we implement a mathematical model that captures both the tension/strain relationship and strain heterogeneity. Our study unveils a new type of mechanical behavior -active superelasticity- that enables epithelial sheets to sustain extreme stretching under constant tension. Els processos fonamentals en desenvolupament i en fisiologia estan determinats per l’estructura tridimensional dels teixits epitelials. Tot i així, l’explicació de com aquests teixits es deformen i es repleguen formant estructures complexes ha restat incerta perquè les seves propietats mecàniques en tres dimensions eren inaccessibles de forma experimental. Mitjançant la combinació de mesures de la tensió epitelial, de la forma i de la pressió luminal amb modelatge matemàtic, mostrem que els teixits de cèl·lules epitelials són materials superelàstics actius. Desenvolupem un nou mètode per produir de forma massiva matrius de doms epitelials (teixit epitelial en forma de cúpula) controlant a la vegada la seva forma i mida a la base. A partir de la mesura de les deformacions tridimensionals del substrat i de la mesura de la curvatura dels doms, obtenim una mesura directa de la pressió luminal i de la tensió epitelial. Amb observacions en escales temporals d’hores podem fer el mapatge de la relació tensió-deformació epitelial, que revela que la tensió es fa constant mentre l’àrea augmenta i es multiplica unes quantes vegades fins arribar a una deformació areal del 300%. Mostrem que aquestes deformacions nominals extremes són acomodades per una deformació de les cèl·lules individuals que és molt heterogènia, amb cèl·lules lleugerament deformades que coexisteixen amb altres que assoleixen el 1000% de deformació areal, aparentment en contradicció amb la uniformitat de la tensió mesurada. Aquesta fenomenologia evoca la superelasticitat, que és un comportament mecànic que s’atribueix generalment a inestabilitats materials microscòpiques en alguns aliatges metàl·lics. Aportem evidències que, en les cèl·lules epitelials, aquesta inestabilitat està desencadenada per una dilució del còrtex d’actina induïda per la deformació i limitada per la xarxa de filaments intermedis. Finalment, implementem un model matemàtic que captura a la vegada la relació tensió-deformació i l’heterogeneïtat en la deformació. El nostre estudi revela un nou tipus de comportament mecànic -la superelasticitat activa- que permet als teixits epitelials poder suportar deformacions extremes mantenint la tensió constant.

show abstract

Monitoring contractility in single cardiomyocytes and whole hearts with bio-integrated microlasers

Cited by 4 publications

References 40 publications

Monitoring contractility in cardiac tissue with cellular resolution using biointegrated microlasers

Monitoring contractility in cardiac tissue with cellular resolution using biointegrated microlasers

Measuring mechanical stress in living tissues

Active superelasticity in three-dimensional epithelia of controlled shape

Contact Info

Product

Resources

About