The force loading rate drives cell mechanosensing through both reinforcement and cytoskeletal softening

Andreu, Ion; Falcones, Bryan; Hurst, Sebastian; Chahare, Nimesh R.; Quiroga, Xarxa; Roux, Anabel‐Lise Le; Kechagia, Jenny Z.; Beedle, Amy E. M.; Elosegui‐Artola, Alberto; Trepat, Xavier; Farré, Ramón; Betz, Timo; Almendros, Isaac; Roca‐Cusachs, Pere

doi:10.1038/s41467-021-24383-3

Cited by 79 publications

(54 citation statements)

References 77 publications

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“…Furthermore, rather than displaying a homeostatic behaviour, the traction stress keeps decreasing even after the activation is stopped. We hypothesize, that this may occur because the actin structures acutely fluidize in response to the local stress increase, as previously reported [39, 40]. Since there is no junction and thus no diffusion barrier in singlets, the imbalance in stress induced by optogenetic activation may lead to a flow of F-actin from the non-activated to the activated region, consistent with our observations (Fig.…”

Section: Resultssupporting

confidence: 91%

Force propagation between epithelial cells depends on active coupling and mechano-structural polarization

Ruppel

Wörthmüller

Misiak

et al. 2022

Preprint

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Cell-generated forces play a major role in coordinating the large-scale behavior of cell assemblies, in particular during development, wound healing and cancer. Mechanical signals propagate faster than biochemical signals, but can have similar effects, especially in epithelial tissues with strong cell-cell adhesion. However, a quantitative description of the transmission chain from force generation in a sender cell, force propagation across cell-cell boundaries, and the concomitant response of receiver cells is missing. For a quantitative analysis of this important situation, here we propose a minimal model system of two epithelial cells on an H-pattern (“cell doublet”). After optogenetically activating RhoA, a major regulator of cell contractility, in the sender cell, we measure the mechanical response of the receiver cell by traction force and monolayer stress microscopies. In general, we find that the receiver cells shows an active response so that the cell doublet forms a coherent unit. However, force propagation and response of the receiver cell also strongly depends on the mechano-structural polarization in the cell assembly, which is controlled by cell-matrix adhesion to the adhesive micropattern. We find that the response of the receiver cell is stronger when the mechano-structural polarization axis is oriented perpendicular to the direction of force propagation, reminiscent of the Poisson effect in passive materials. We finally show that the same effects are at work in small tissues. Our work demonstrates that cellular organization and active mechanical response of a tissue is key to maintain signal strength and leads to the emergence of elasticity, which means that signals are not dissipated like in a viscous system, but can propagate over large distances.

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Section: Resultssupporting

confidence: 91%

Force propagation between epithelial cells depends on active coupling and mechano-structural polarization

Ruppel

Wörthmüller

Misiak

et al. 2022

Preprint

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show abstract

“…According to the molecular clutch hypothesis, contractile forces are only optimally transmitted if the whole system (from actin microfilaments to these adaptor proteins) is engaged. Otherwise, the adhesion complex cannot maintain high force transmission because of an unstructured or fluidized, softened cytoskeleton [ 150 ]. Also, preliminary reports from Newman and colleagues [ 151 ] showed that IACs in protrusions enable actomyosin-mediated force transmission to the nucleus.…”

Section: Mechanics Of Cell Migrationmentioning

confidence: 99%

Unravelling cell migration: defining movement from the cell surface

Merino-Casallo

Gómez‐Benito

Hervas-Raluy

et al. 2022

Cell Adhesion & Migration

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Cell motility is essential for life and development. Unfortunately, cell migration is also linked to several pathological processes, such as cancer metastasis. Cells’ ability to migrate relies on many actors. Cells change their migratory strategy based on their phenotype and the properties of the surrounding microenvironment. Cell migration is, therefore, an extremely complex phenomenon. Researchers have investigated cell motility for more than a century. Recent discoveries have uncovered some of the mysteries associated with the mechanisms involved in cell migration, such as intracellular signaling and cell mechanics. These findings involve different players, including transmembrane receptors, adhesive complexes, cytoskeletal components , the nucleus, and the extracellular matrix. This review aims to give a global overview of our current understanding of cell migration.

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“…Further investigations will require to develop computational and mathematical models at the filament level to consider forces and deformations of individual cytoskeletal components of neuronal cells ( Rutkowski and Vavylonis, 2021 ). Moreover, additional work using mechanobiology assays, such as substrate stretching and optical tweezers, are required to gain quantitative insight into the role of the rate of force application, which has been recently identified as a key component of the mechanosensing mechanism in mouse embryonic fibroblasts ( Andreu et al, 2021 ).…”

Section: Mechanobiology Of Brain Cellsmentioning

confidence: 99%

Multiscale Mechanobiology in Brain Physiology and Diseases

Procès

Luciano

Kalukula

et al. 2022

Front. Cell Dev. Biol.

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Increasing evidence suggests that mechanics play a critical role in regulating brain function at different scales. Downstream integration of mechanical inputs into biochemical signals and genomic pathways causes observable and measurable effects on brain cell fate and can also lead to important pathological consequences. Despite recent advances, the mechanical forces that influence neuronal processes remain largely unexplored, and how endogenous mechanical forces are detected and transduced by brain cells into biochemical and genetic programs have received less attention. In this review, we described the composition of brain tissues and their pronounced microstructural heterogeneity. We discuss the individual role of neuronal and glial cell mechanics in brain homeostasis and diseases. We highlight how changes in the composition and mechanical properties of the extracellular matrix can modulate brain cell functions and describe key mechanisms of the mechanosensing process. We then consider the contribution of mechanobiology in the emergence of brain diseases by providing a critical review on traumatic brain injury, neurodegenerative diseases, and neuroblastoma. We show that a better understanding of the mechanobiology of brain tissues will require to manipulate the physico-chemical parameters of the cell microenvironment, and to develop three-dimensional models that can recapitulate the complexity and spatial diversity of brain tissues in a reproducible and predictable manner. Collectively, these emerging insights shed new light on the importance of mechanobiology and its implication in brain and nerve diseases.

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The force loading rate drives cell mechanosensing through both reinforcement and cytoskeletal softening

Cited by 79 publications

References 77 publications

Force propagation between epithelial cells depends on active coupling and mechano-structural polarization

Force propagation between epithelial cells depends on active coupling and mechano-structural polarization

Unravelling cell migration: defining movement from the cell surface

Multiscale Mechanobiology in Brain Physiology and Diseases

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