Mechanical communication in fibrosis progression

Yi, Long; Niu, Yudi; Liang, Kaini; Du, Yanan

doi:10.1016/j.tcb.2021.10.002

Cited by 108 publications

(65 citation statements)

References 119 publications

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“…These deformations can form a visible fibrous band of aligned and dense fibers coupling the communicating cells mechanically, influencing the cells' internal molecular state 15 and active response 16 . This long-range mechanical intercellular communication through the ECM (termed here cell-ECM-cell communication) was observed for cells embedded in synthetic 2,7 and biopolymer fibrous matrices 1, 3-6, 8, 9, 11-13 and are thought to play a key role in tissue regeneration and disease progression 5,[16][17][18][19][20][21][22][23] . In-vivo, fiber alignment bands can serve as ECM 'tracks' for cell migration with potential roles in wound healing, cancer metastasis and fibrosis 24,25 .…”

Section: Introductionmentioning

confidence: 89%

Inference of long-range cell-cell force transmission from ECM remodeling fluctuations

Nahum

Koren

Natan

et al. 2020

Preprint

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Cells sense, manipulate and respond to the mechanical properties of their microenvironment in a plethora of physiological processes, yet whether and how cells interpret environmental cues to communicate with distant cells is mostly unknown. We present a computational method to systematically infer and quantify long-range mechanical cell-cell communication through the extracellular matrix (cell-ECM-cell communication). By correlating local ECM remodeling fluctuations, in finite element simulations and live 3D imaging of fibroblasts embedded in fibrin gels, our method matched pairs of communicating cells with high accuracy, and identified whether and to what extent one cell was influenced by its communication partner. Using this method, we revealed that cells actively respond to the mechanical signal that they sense from the other cell, amplifying the formation of a dense fibrin band between the communicating cells. Our method sets the stage to measure the fundamental aspects of intercellular long-range mechanical communication in physiological contextes and may provide a new functional readout for high content 3D image-based screening.

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Section: Introductionmentioning

confidence: 89%

Inference of long-range cell-cell force transmission from ECM remodeling fluctuations

Nahum

Koren

Natan

et al. 2020

Preprint

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“…Mechanical cues in fibrosis progression can be both the cause and result of fibroblast activation [ 107 , 108 ]. Excessive mechanical stress could be one of the major factors in IDD [ 109 ] resulting in over-activation of TGF-β [ 86 ], YAP/TAZ-mediated cell apoptosis [ 110 ] and inflammatory activation, both in vitro [ 102 , 104 , 111 ] and in vivo [ 102 , 112 ].…”

Section: Regulation Of Np Fibrosismentioning

confidence: 99%

“…TRPC1, TRPV4 and TRPM7 have mechanosensing functions and were found to be expressed in disc cells [ 108 , 116 ]. A compelling role of paratensile signaling in mechanotransdution has recently been suggested [ 107 ]. Traction forces could be directed through the matrix fibers and further activate DDR2 and calcium influx for MRTF-A shuffling and myofibroblast generation [ 121 ].…”

Section: Regulation Of Np Fibrosismentioning

confidence: 99%

Current Perspectives on Nucleus Pulposus Fibrosis in Disc Degeneration and Repair

Sun

Lyu

et al. 2022

IJMS

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A growing body of evidence in humans and animal models indicates an association between intervertebral disc degeneration (IDD) and increased fibrotic elements in the nucleus pulposus (NP). These include enhanced matrix turnover along with the abnormal deposition of collagens and other fibrous matrices, the emergence of fibrosis effector cells, such as macrophages and active fibroblasts, and the upregulation of the fibroinflammatory factors TGF-β1 and IL-1/-13. Studies have suggested a role for NP cells in fibroblastic differentiation through the TGF-βR1-Smad2/3 pathway, inflammatory activation and mechanosensing machineries. Moreover, NP fibrosis is linked to abnormal MMP activity, consistent with the role of matrix proteases in regulating tissue fibrosis. MMP-2 and MMP-12 are the two main profibrogenic markers of myofibroblastic NP cells. This review revisits studies in the literature relevant to NP fibrosis in an attempt to stratify its biochemical features and the molecular identity of fibroblastic cells in the context of IDD. Given the role of fibrosis in tissue healing and diseases, the perspective may provide new insights into the pathomechanism of IDD and its management.

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“…Simultaneously, the ECM is continuously remodelled by cells as they exert these traction forces 5 during cell migration and morphological re-arrangement 6 . Anomalies in the mechanical properties of the ECM play significant roles in the development of pathologies such as cancer 7 and fibrosis 8 , often establishing barriers to therapeutic intervention 9 . Modelling and understanding the cellular influence on ECM biomechanics are challenging processes given the wide range of mechanical environments experienced in health and disease.…”

Section: Introductionmentioning

confidence: 99%

OptoRheo: Simultaneousin situmicro-mechanical sensing and imaging of live 3D biological systems

Mendonça

Lis-Slimak

Matheson

et al. 2022

Preprint

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Biomechanical cues from the extracellular matrix (ECM) are essential for directing many cellular processes, from normal development and repair to disease progression. To better understand cell-matrix interactions, we have developed an optical instrument combining light sheet fluorescence microscopy with particle tracking microrheology. We name this new instrument OptoRheo. OptoRheo lets us image cells in 3D as they proliferate over several days while simultaneously sensing the biomechanical properties of the surrounding extracellular and pericellular matrix at a sub-cellular scale. OptoRheo can be used in two operational modalities to extend the dynamic range of microrheology measurements, making the instrument suitable for different cell culture systems. We corroborated this by characterising the ECM surrounding live breast cancer cells in two distinct culture systems, 3D hydrogels and suspension culture. This cutting-edge instrument will transform the exploration of drug transport through complex cell culture matrices and optimise the design of the next-generation disease models.

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Mechanical communication in fibrosis progression

Cited by 108 publications

References 119 publications

Inference of long-range cell-cell force transmission from ECM remodeling fluctuations

Inference of long-range cell-cell force transmission from ECM remodeling fluctuations

Current Perspectives on Nucleus Pulposus Fibrosis in Disc Degeneration and Repair

OptoRheo: Simultaneousin situmicro-mechanical sensing and imaging of live 3D biological systems

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