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End date: 2022 × Start date: 2022 × Type: Text × Publisher: Lausanne : Frontiers Media × WGL Institute: INM ×

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Now showing 1 - 5 of 5
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    On the adhesion between thin sheets and randomly rough surfaces
    (Lausanne : Frontiers Media, 2022) Wang , Anle; Müser, Martin H.
    Thin, elastic sheets are well known to adapt to rough counterfaces, whereby adhesive interactions and pull-off stresses σp can be significant, yet no generally applicable, quantitative guideline has been suggested hitherto as to when a sheet should be considered thin enough to be sticky. Using computer simulations, we find that the dependence of σp on surface energy γ has a high and a low-pull-off-stress regime. For randomly rough surfaces, we locate the dividing line at the point, where γ is approximately half the elastic energy per unit area needed to make conformal contact, which is the same ratio as for semi-infinite elastic solids. This rule of thumb also applies to a certain degree for single-wavelength roughness, in which case the transition from low to high stickiness occurs when at the moment of maximum tension contact is not only broken at the height maxima but also at the saddle points.
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    Unspecific CTL Killing Is Enhanced by High Glucose via TNF-Related Apoptosis-Inducing Ligand
    (Lausanne : Frontiers Media, 2022) Yang, Wenjuan; Denger, Andreas; Diener, Caroline; Küppers, Frederic; Soriano-Baguet, Leticia; Schäfer, Gertrud; Yanamandra, Archana K.; Zhao, Renping; Knörck, Arne; Schwarz, Eva C.; Hart, Martin; Lammert, Frank; Roma, Leticia Prates; Brenner, Dirk; Christidis, Grigorios; Helms, Volkhard; Meese, Eckart; Hoth, Markus; Qu, Bin
    TNF-related apoptosis inducing ligand (TRAIL) is expressed on cytotoxic T lymphocytes (CTLs) and TRAIL is linked to progression of diabetes. However, the impact of high glucose on TRAIL expression and its related killing function in CTLs still remains largely elusive. Here, we report that TRAIL is substantially up-regulated in CTLs in environments with high glucose (HG) both in vitro and in vivo. Non-mitochondrial reactive oxygen species, NFκB and PI3K/Akt are essential in HG-induced TRAIL upregulation in CTLs. TRAILhigh CTLs induce apoptosis of pancreatic beta cell line 1.4E7. Treatment with metformin and vitamin D reduces HG-enhanced expression of TRAIL in CTLs and coherently protects 1.4E7 cells from TRAIL-mediated apoptosis. Our work suggests that HG-induced TRAILhigh CTLs might contribute to the destruction of pancreatic beta cells in a hyperglycemia condition.
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    Cinobufacini Injection Inhibits the Proliferation of Triple-Negative Breast Cancer Through the Pin1-TAZ Signaling Pathway
    (Lausanne : Frontiers Media, 2022) Kong, Lu; Liu, Xu; Yu, Bing; Yuan, Ye; Zhao, Qianru; Chen, Yuru; Qu, Bin; Du, Xue; Tian, Xiaoxuan; Shao, Rui; Wang, Yu
    Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer (BC), which is characterized by the total absence of human epidermal growth factor receptor 2 (HER2), progesterone receptor (PR), and estrogen receptor (ER) expression. Cinobufacini injection (CI) is the aqueous extract from the dry skin of Bufo gargarizans, which is broadly used for the treatment of malignant tumors. However, the potential mechanism of CI against TNBC has not been fully revealed. In this study, we found that CI inhibited the proliferation of MDA-MB-231 and 4T1 cells in a time- and dose-dependent manner. RNA-seq data showed that downregulated and upregulated genes were mainly enriched in biological processes related to tumor cell proliferation, including cell cycle arrest and regulation of apoptosis signaling pathways. Indeed, after CI treatment, the protein level of CDK1 and Bcl-2/Bax decreased, indicating that CI induced the cell cycle of MDA-MB-231 arrest in the G2/M phase and increased the rate of apoptosis. Meanwhile, CI significantly inhibited the growth of tumor in vivo, and RNA-seq data showed that the TAZ signaling pathway played a vital role after CI treatment. Both immunohistochemistry and Western blot analysis confirmed the downregulation of Pin1 and TAZ, caused by CI treatment. Furthermore, the bioinformatics analysis indicated that Pin1 and TAZ were indeed elevated in TNBC patients, with poor staging, classification, and patient survival rate. In conclusion, CI effectively inhibited the proliferation of TNBC in vitro and in vivo and induced their apoptosis and cycle arrest through the Pin1–TAZ pathway.
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    Light-Sheet Scattering Microscopy to Visualize Long-Term Interactions Between Cells and Extracellular Matrix
    (Lausanne : Frontiers Media, 2022) Zhou, Xiangda; Zhao, Renping; Yanamandra, Archana K.; Hoth, Markus; Qu, Bin
    Visualizing interactions between cells and the extracellular matrix (ECM) mesh is important to understand cell behavior and regulatory mechanisms by the extracellular environment. However, long term visualization of three-dimensional (3D) matrix structures remains challenging mainly due to photobleaching or blind spots perpendicular to the imaging plane. Here, we combine label-free light-sheet scattering microcopy (LSSM) and fluorescence microscopy to solve these problems. We verified that LSSM can reliably visualize structures of collagen matrices from different origin including bovine, human and rat tail. The quality and intensity of collagen structure images acquired by LSSM did not decline with time. LSSM offers abundant wavelength choice to visualize matrix structures, maximizing combination possibilities with fluorescently-labelled cells, allowing visualizing of long-term ECM-cell interactions in 3D. Interestingly, we observed ultrathin thread-like structures between cells and matrix using LSSM, which were not observed by normal fluorescence microscopy. Transient local alignment of matrix by cell-applied forces can be observed. In summary, LSSM provides a powerful and robust approach to investigate the complex interplay between cells and ECM.
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    Vitronectin-based hydrogels recapitulate neuroblastoma growth conditions
    (Lausanne : Frontiers Media, 2022) Monferrer, Ezequiel; Dobre, Oana; Trujillo, Sara; González Oliva, Mariana Azevedo; Trubert-Paneli, Alexandre; Acevedo-León, Delia; Noguera, Rosa; Salmeron-Sanchez, Manuel
    The tumor microenvironment plays an important role in cancer development and the use of 3D in vitro systems that decouple different elements of this microenvironment is critical for the study of cancer progression. In neuroblastoma (NB), vitronectin (VN), an extracellular matrix protein, has been linked to poor prognosis and appears as a promising therapeutic target. Here, we developed hydrogels that incorporate VN into 3D polyethylene glycol (PEG) hydrogel networks to recapitulate the native NB microenvironment. The stiffness of the VN/PEG hydrogels was modulated to be comparable to the in vivo values reported for NB tissue samples. We used SK-N-BE (2) NB cells to demonstrate that PEGylated VN promotes cell adhesion as the native protein does. Furthermore, the PEGylation of VN allows its crosslinking into the hydrogel network, providing VN retention within the hydrogels that support viable cells in 3D. Confocal imaging and ELISA assays indicate that cells secrete VN also in the hydrogels and continue to reorganize their 3D environment. Overall, the 3D VN-based PEG hydrogels recapitulate the complexity of the native tumor extracellular matrix, showing that VN-cell interaction plays a key role in NB aggressiveness, and that VN could potentially be targeted in preclinical drug studies performed on the presented hydrogels.