ACS Omega
·
2024
·
IF 3.7
Ninan Zhang,Ruifan Lin,Honglin Xu,Xianghong Jing,Hongwei Zhou,Xiaoxiao Wen,Qi Xie
Curcumin, a compound derived from turmeric, is traditionally utilized in East Asian medicine for treating various health conditions, including epilepsy. Despite its involvement in numerous cellular signaling pathways, the specific mechanisms and targets of curcumin in epilepsy treatment have remained unclear. Our study focused on identifying the primary targets and functional pathways of curcumin in the brains of epileptic mice. Using drug affinity responsive target stabilization (DARTS) and affinity chromatography, we identified key targets in the mouse brain, revealing 232 and 70 potential curcumin targets, respectively. Bioinformatics analysis revealed a strong association of these proteins with focal adhesions and cytoskeletal components. Further experiments using DARTS, along with immunofluorescence staining and cell migration assays, confirmed curcumin’s ability to regulate the dynamics of focal adhesions and influence cell migration. This study not only advances our understanding of curcumin’s role in epilepsy treatment but also serves as a model for identifying therapeutic targets in neurological disorders.
研究领域:
神经科学
·
药理学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
CELL BIOLOGY INTERNATIONAL
·
2021
·Vol. 45
·期 9
·1926-1934
·
IF 3.612
Yan Li,Zhongjie Qin,Lin Zhou,Khawar Ali Shahzad,Delin Xia
In the treatment of cardiovascular diseases, vascular scaffold materials play an extremely important role. The appropriate substrate chemistries and 15 dynes/cm 2 physiological fluid shear stress (FSS) are both required to ensure normal physiological activity of human umbilical vein endothelial cells (HUVECs). The present study reported the collective influence of substrate chemistries and FSS on HUVECs in the sense of its biological functions. The CH 3 , NH 2 , and OH functional groups were adopted to offer a variety of substrate chemistries on glass slides by the technology of self-assembled monolayers, whereas FSS was generated by a parallel-plate fluid flow system. Substrate chemistries on its own by no means had noticeable effects on eNOS, ATP, NO, and PGI 2 expressions, while FSS stimuli enhanced their production. While substrate chemistries, as well as FSS, were both exerted, the releases of ATP, NO, and PGI 2 were dependent on substrate chemistries. Study of F-actin organization and focal adhesions (FAs) formation of HUVECs before FSS exposure proves that F-action organization and FAs formation followed similar chemistry-dependence. Hereby proposed a feasible mechanism, that is, the F-actin organization and FAs formation of HUVECs are controlled by substrate chemistries, further advancing the modulation of FSS-triggered responses of HUVECs.
研究领域:
生物医学工程
·
细胞生物学
·
组织工程
✓ 已验证
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2023
·
IF 10
Zhao Wei,Jingyi Liu,Yuanbo Jia,Meng Lei,Songbai Zhang,Pan Xi,Yufei Ma,Min Zhang,Jinlu Ma,Lin Wang,Hui Guo,Feng Xu
The fiber structures of tumor microenvironment (TME) are well-known in regulating tumor cell behaviors, and the plastic remolding of TME has recently been suggested to enhance tumor metastasis as well. However, the interrelationship between the fiber microarchitecture and matrix plasticity are inextricable by existing in vitro models. The individual roles of fiber microarchitecture and matrix plasticity in tuning tumor cell behaviors remain elusive. In this study, we develop a interpenetrating collagen-alginate hydrogel platform with independently tunable matrix plasticity and fiber microarchitecture through an interpenetrating strategy of alginate networks and collagen I networks. With this hydrogel platform, we demonstrate that tumor cells in high plasticity hydrogels are more extensive and aggressive than in low plasticity hydrogels and fiber structures only has influence in high plasticity hydrogels. We further elucidate the underlying mechanisms through analyzing the distribution of forces within the matrix and tracking the focal adhesions (FAs) and find that highly plastic hydrogels can activate the FAs formation, whereas the maturation and stability of FAs are dominated by fiber dispersion. This study not only establishes new ideas on how cells interact with TME cues but also would help to further finely tailor engineered hydrogel platforms for studying tumor behaviors in vitro. This article is protected by copyright. All rights reserved
研究领域:
生物材料
·
生物力学
·
癌症生物学
·
细胞生物学
·
组织工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMACROMOLECULES
·
2021
·
IF 6.988
Jinfeng Wang,Junyao Li,Juan Liu,Manping Lin,Shilong Mao,Yuanliang Wang,Yanfeng Luo
Osteoblasts actively generate cell traction force (CTF) to sense chemical and mechanical microenvironments. Fluid shear stress (FSS) is a principle mechanical stimulus for bone modeling/remodeling. FSS and CTF share common interconnected elements for force transmission, among which the role of the protein-material interfacial force (Fad) remains unclear. Here, we found that, on the low Fad surface (5.47 ± 1.31 pN/FN), CTF overwhelmed Fad to partially desorb FN, and FSS exacerbated the desorption, resulting in disassembly of the actin cytoskeleton and focal adhesions (FAs) to reduce CTF and establishment of a new mechanical balance at the FN-material interface. Contrarily, on the high Fad surface (27.68 ± 5.24 pN/FN), pure CTF or the combination of CTF and FSS induced no FN desorption, and FSS promoted assembly of actin cytoskeletons and disassembly of FAs, regaining new mechanical balance at the cell-FN interface. These results indicate that Fad is a mechanical regulator for transmission of CTF and FSS, which has never been reported before.
研究领域:
生物力学
·
细胞生物学
·
组织工程
·
材料科学
✓ 已验证
DOI
PubMed
高影响因子
MACROMOLECULAR MATERIALS AND ENGINEERING
·
2020
·Vol. 305
·期 4
·1900759
·
IF 3.853
Tingting Yu,Ke Hu,Qiufan Xu,Xueqin Xu,Chunyue Du,Yinyi Zhao,Sen Yan,Wei Wang,Shijia Tang,Shen Yue,Xiya Zhang,Danlei Wang,Feimin Zhang,Steven Yan Cheng,Ning Gu
The biophysical factors of microenvironments have increasingly been recognized as playing key roles in driving cell functions along with biochemical cues. However, current synthetic extracellular matrix materials with tunable biophysical properties are both costly and technically complicated to prepare, therefore limiting their application in the molecular biology field. Herein, an interpenetration hydrogel group with gradient stiffness and cell anchor points is developed, and the matrix stiffness and adhesion property functions as key regulators to determine the final output of Sonic Hedgehog (Shh) signaling is reported. Specifically, it is shown that the spreading areas of mouse embryonic fibroblasts are mainly regulated by stiffness of the matrix. The Shh-induced Gli1 expression also increases with the cell spreading area. Finally, this work shows that b1-integrin and focal adhesion kinase, respectively, act as sensors of matrix stiffness and adhesion properties, demonstrating the significance of the precise regulation of Shh signaling by cellular microenvironments. These results demonstrate the feasibility of using this hydrogel platform to study the impact of biophysical changes of the microenvironment on particular cellular signal pathways, and can potentially be applied in low-cost, high throughput screening of signal pathways which are responsive to the biophysical changes of microenvironments.
研究领域:
生物材料
·
细胞生物学
·
分子生物学
·
生物物理学
✓ 已验证
产品关联
DOI
高影响因子
Nature Communications
·
2023
·Vol. 14
·期 1
·1-16
·
IF 16.6
Wei Zhao,Lei Meng,Wang Yaohui,Xie Yizhou,Xie Xueyong,Lan Dongwei,Jia Yuanbo,Liu Jingyi,Ma Yufei,Cheng Bo,Gerecht Sharon,Xu Feng
The endothelial cell (EC) outgrowth in both vasculogenesis and angiogenesis starts with remodeling surrounding matrix and proceeds with the crosstalk between cells for the multicellular vasculature formation. The mechanical plasticity of matrix, defined as the ability to permanently deform by external traction, is pivotal in modulating cell behaviors. Nevertheless, the implications of matrix plasticity on cell-to-cell interactions during EC outgrowth, along with the molecular pathways involved, remain elusive. Here we develop a collagen-hyaluronic acid based hydrogel platform with tunable plasticity by using compositing strategy of dynamic and covalent networks. We show that although the increasing plasticity of the hydrogel facilitates the matrix remodeling by ECs, the largest tubular lumens and the longest invading distance unexpectedly appear in hydrogels with medium plasticity instead of the highest ones. We unravel that the high plasticity of the hydrogels promotes stable integrin cluster of ECs and recruitment of focal adhesion kinase with an overenhanced contractility which downregulates the vascular endothelial cadherin expression and destabilizes the adherens junctions between individual ECs. Our results, further validated with mathematical simulations and in vivo angiogenic tests, demonstrate that a balance of matrix plasticity facilitates both cell-matrix binding and cell-to-cell adherens, for promoting vascular assembly and invasion.
研究领域:
生物材料
·
组织工程
·
细胞生物学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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