An in vitro correlation of metastatic capacity and dual mechanostimulation

Indra, Indrajyoti; Gasparski, Alexander N.; Beningo, Karen A.

doi:10.1371/journal.pone.0207490

Cited by 4 publications

(4 citation statements)

References 42 publications

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“…Moreover, knowledge of the fundamental mechanisms of the mechanical characteristics of the microenvironment contributes to advances in the treatment of injuries, malignancies, and diseases associated with alterations in the mechanophenotype of the extracellular matrix. A recently developed biophysical technique is a method that paves the way for monitoring both extracellular stiffness and dynamic mechanical stress by cladding cells on substrates of varying stiffness in conjunction with transient stretching of the substrate or "tugging" by magnetic manipulations [423].…”

Section: Discussionmentioning

confidence: 99%

Bidirectional Mechanical Response Between Cells and Their Microenvironment

Mierke

2021

Front. Phys.

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Cell migration and invasion play a role in many physiological and pathological processes and are therefore subject of intensive research efforts. Despite of the intensively investigated biochemical processes associated with the migration and invasion of cells, such as cancer cells, the contribution of mechanobiological processes to the migratory capacity of cells as well as the role of physical polymeric phase transitions is not yet clearly understood. Unfortunately, these experiments are not very informative because they completely disregard the influence of the three-dimensional cell environment. Despite this data situation, it was possible to adequately demonstrate that there exists a direct mechanical interplay between cells and their microenvironment in both directions, where both elements can be mechanically altered by one another. In line with these results, it has turned out that the mechanobiological molecular processes through which cells interact with each other and additionally sense their nearby microenvironment have an impact on cellular functions such as cellular motility. The mechanotransduction processes have become the major focus of biophysical research and thereby, diverse biophysical approaches have been developed and improved to analyze the mechanical properties of individual cells and extracellular matrix environments. Both, the cell mechanics and matrix environment mechanics regulate the cell migration types in confined microenvironments and hence it seems to be suitable to identify and subsequently present a common bidirectional interplay between cells and their matrix environment. Moreover, hallmarks of the mechanophenotype of invasive cells and extracellular matrices can be defined. This review will point out how on the one hand the intracellular cytoskeletal architecture and on the other hand the matrix architecture contribute to cellular stiffness or contractility and thereby determines the migratory phenotype and subsequently the emergence of a distinct migration mode. Finally, in this review it is discussed whether universal hallmarks of the migratory phenotype can be defined.

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Section: Discussionmentioning

confidence: 99%

Bidirectional Mechanical Response Between Cells and Their Microenvironment

Mierke

2021

Front. Phys.

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“…In other studies using a flexible silicone culture system, non-tumorigenic mammary HC11 cells subjected to mechanical stretch responded with increased c-fos protein expression (after 60 min of mechanical strain) and ERK1/2 phosphorylation (after 5 min of mechanical strain) [ 131 ]. Finally, one method sets the stage for monitoring both extracellular stiffness and dynamic mechanical stress using cells plated on substrates of different stiffness coupled to transient substrate stretch or “tugging” via magnetic manipulation [ 209 ]. Following similar approaches, it may be possible to experimentally define novel signaling mechanisms by which breast cancer cells integrate acute mechanical cues, and set the foundation for further drug discovery.…”

Section: Discussionmentioning

confidence: 99%

The Mechanical Microenvironment in Breast Cancer

Pratt

Lee

Martin

2020

Cancers

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Mechanotransduction is the interpretation of physical cues by cells through mechanosensation mechanisms that elegantly translate mechanical stimuli into biochemical signaling pathways. While mechanical stress and their resulting cellular responses occur in normal physiologic contexts, there are a variety of cancer-associated physical cues present in the tumor microenvironment that are pathological in breast cancer. Mechanistic in vitro data and in vivo evidence currently support three mechanical stressors as mechanical modifiers in breast cancer that will be the focus of this review: stiffness, interstitial fluid pressure, and solid stress. Increases in stiffness, interstitial fluid pressure, and solid stress are thought to promote malignant phenotypes in normal breast epithelial cells, as well as exacerbate malignant phenotypes in breast cancer cells.

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“…They used a combination of substrates with varying degrees of compliance and triggered a cyclic deformation of the matrix using a single magnetic bead. 22 Aiming to test the effect of local deformation of the ECM on cells residing there, further approaches have been developed but are often focused on individual cells and are not compatible with established 3D cancer invasion assays. 23 In a recent study by Shou et al, 3D magnetic hydrogels were developed to study the effect of stiffness changes on embedded cancer spheroids.…”

Section: Introductionmentioning

confidence: 99%

Magnetically Controlled Cyclic Microscale Deformation ofIn VitroCancer Invasion Models

Asgeirsson

Mehta

Hesse

et al. 2023

Preprint

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Mechanical cues play an important role in the metastatic cascade of cancer. Three-dimensional (3D) tissue matrices with tunable stiffness have been extensively used as model systems of the tumor microenvironment for physiologically relevant studies. Tumor-associated cells actively deform these matrices, providing mechanical cues to other cancer cells residing in the tissue. Mimicking such dynamic deformation in the surrounding tumor matrix may help clarify the effect of local strain on cancer cell invasion. Remotely controlled microscale magnetic actuation of such 3D in vitro systems is a promising approach, offering a non-invasive means for in situ interrogation. Here, we investigate the influence of cyclic deformation on tumor spheroids embedded in matrices, continuously exerted for days by cell-sized anisotropic magnetic probes, referred to as uRods. Particle velocimetry analysis revealed the spatial extent of matrix deformation produced in response to a magnetic field, which was found to be on the order of 200 um, resembling strain fields reported to originate from contracting cells. Intracellular calcium influx was observed in response to cyclic actuation, as well as an influence on cancer cell invasion from 3D spheroids, as compared to unactuated controls. Localized actuation at one side of a tumor spheroid tended to result in anisotropic invasion toward the uRods causing the deformation. In summary, our approach offers a strategy to test and control the influence of non-invasive micromechanical cues on cancer cell invasion and metastasis.

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An in vitro correlation of metastatic capacity and dual mechanostimulation

Cited by 4 publications

References 42 publications

Bidirectional Mechanical Response Between Cells and Their Microenvironment

Bidirectional Mechanical Response Between Cells and Their Microenvironment

The Mechanical Microenvironment in Breast Cancer

Magnetically Controlled Cyclic Microscale Deformation ofIn VitroCancer Invasion Models

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