Whole tissue and single cell mechanics are correlated in human brain tumors

Sauer, Frank; Fritsch, Anatol; Grosser, Steffen; Pawlizak, Steve; Kießling, T.; Reiss-Zimmermann, M; Shahryari, Mehrgan; Müller, Wolf; Hoffmann, Karl‐Titus; Käs, Josef A.; Sack, Ingolf

doi:10.1039/d1sm01291f

Cited by 15 publications

(9 citation statements)

References 44 publications

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“…This supports the in vivo MRE results that GB is softer but more solid‐like than MEN, as depicted in Figure 2. Additionally, our recent study found a correlation between single cell and bulk properties in GB but not in MEN, [ 118 ] which could be another result of the lack of fibrous ECM in GB.…”

Section: Discussionmentioning

confidence: 99%

Changes in Tissue Fluidity Predict Tumor Aggressiveness In Vivo

Sauer¹,

Grosser

Shahryari

et al. 2023

Advanced Science

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Cancer progression is caused by genetic changes and associated with various alterations in cell properties, which also affect a tumor's mechanical state. While an increased stiffness has been well known for long for solid tumors, it has limited prognostic power. It is hypothesized that cancer progression is accompanied by tissue fluidization, where portions of the tissue can change position across different length scales. Supported by tabletop magnetic resonance elastography (MRE) on stroma mimicking collagen gels and microscopic analysis of live cells inside patient derived tumor explants, an overview is provided of how cancer associated mechanisms, including cellular unjamming, proliferation, microenvironment composition, and remodeling can alter a tissue's fluidity and stiffness. In vivo, state‐of‐the‐art multifrequency MRE can distinguish tumors from their surrounding host tissue by their rheological fingerprints. Most importantly, a meta‐analysis on the currently available clinical studies is conducted and universal trends are identified. The results and conclusions are condensed into a gedankenexperiment about how a tumor can grow and eventually metastasize into its environment from a physics perspective to deduce corresponding mechanical properties. Based on stiffness, fluidity, spatial heterogeneity, and texture of the tumor front a roadmap for a prognosis of a tumor's aggressiveness and metastatic potential is presented.

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Section: Discussionmentioning

confidence: 99%

Changes in Tissue Fluidity Predict Tumor Aggressiveness In Vivo

Sauer¹,

Grosser

Shahryari

et al. 2023

Advanced Science

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“…Starting on the bulk tissue level, we performed tabletop MRE [28][29][30] on centimeter sized vital tumor explants, from resected tissue obtained from cervical and mammary carcinomas to quantify the macroscopic average viscoelastic properties of the tumor (Figure 1). Soft tissues and cells often exhibit a distinctive power-law viscoelastic response arising from a broad distribution of time-scales present in their complex internal structure.…”

Section: Carcinomas Are Not Necessarily Stiffer Than the Surrounding Tissue Matrixmentioning

confidence: 99%

Rigid tumors contain soft cancer cells

Fuhs

Wetzel²,

Fritsch

et al. 2021

Preprint

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Palpation, as already mentioned in the ancient Egyptian medical text Ebers Papyrus, utilizes that solid tumors are stiffer than the surrounding tissue. However, cancer cell lines tend to soften, which may intuitively foster invasion by enhancing the ability of cancer cells to squeeze through dense tissue. This paradox raises questions besides the oxymoron itself: Does softness emerge from adaptation to the external microenvironment? Or are soft cells already present inside a rigid primary tumor mass to support cancer cell unjamming? We investigate primary tumor explants from patients with breast and cervix carcinomas on multiple length scales from the tissue level down to single cells. We find that primary tumors are highly heterogeneous in their mechanical properties. From the tissue level this heterogeneity persists down to the scale of individual cells in cancer cell clusters, resulting in a broad distribution of cell rigidities with a higher fraction of softer, more squeezable cells. Plus, squeezed cell shapes correlate with cancer cell motility. Mechanical modelling based on patient data reveals that a tumor mass as a whole is able to maintain a rigid, solid behavior even when it contains a significant fraction of very soft cells. Cell softening induced cancer cell unjamming generates heterogeneous cancer cell clusters with a solid backbone of rigid cells surrounded by soft motile cells.

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“…The mechanical properties of cells reflect both the physiological development of cellular processes as well as signal the emergence of pathological states. Changes in mechanical properties have been noticed in differentiating cells (Maloney et al, 2010; Steward & Kelly, 2015), cell migration (Lautenschläger et al, 2009), throughout the cell cycle (Otto et al, 2015), as well as in cells undergoing oncological processes (Frank Sauer et al, 2021; Lekka & Pabijan, 2019), or responding to inflammatory conditions (Ekpenyong et al, 2015). These and other studies have established the importance of mechanical properties as a sensitive biomarker of cellular response to a dynamic microenvironment.…”

Section: Introductionmentioning

confidence: 99%

Cell‐surface contacts determine volume and mechanical properties of human embryonic kidney 293 T cells

et al. 2022

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Alterations in the organization of the cytoskeleton precede the escape of adherent cells from the framework of cell-cell and cell-matrix interactions into suspension.With cytoskeletal dynamics being linked to cell mechanical properties, many studies elucidated this relationship under either native adherent or suspended conditions. In contrast, tethered cells that mimic the transition between both states have not been the focus of recent research. Using human embryonic kidney 293 T cells we investigated all three conditions in the light of alterations in cellular shape, volume, as well as mechanical properties and relate these findings to the level, structure, and intracellular localization of filamentous actin (F-actin). For cells adhered to a substrate, our data shows that seeding density affects cell size but does not alter their elastic properties. Removing surface contacts leads to cell stiffening that is accompanied by changes in cell shape, and a reduction in cellular volume but no alterations in F-actin density. Instead, we observe changes in the organization of F-actin indicated by the appearance of blebs in the semi-adherent state. In summary, our work reveals an interplay between molecular and mechanical alterations when cells detach from a surface that is mainly dominated by cell morphology.

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Whole tissue and single cell mechanics are correlated in human brain tumors

Abstract: Biomechanical changes are critical for cancer progression.

Cited by 15 publications

References 44 publications

Changes in Tissue Fluidity Predict Tumor Aggressiveness In Vivo

Changes in Tissue Fluidity Predict Tumor Aggressiveness In Vivo

Rigid tumors contain soft cancer cells

Cell‐surface contacts determine volume and mechanical properties of human embryonic kidney 293 T cells

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