JOURNAL OF NANOBIOTECHNOLOGY
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2022
·Vol. 20
·期 1
·1-13
·
IF 9.429
Wang Yongtao,Wang Nana,Yang Yingjun,Chen Yazhou,Zhang Zhengguo
Gene transfection was supposed to be the most promising technology to overcome the vast majority of diseases and it has been popularly reported in clinical applications of gene therapy. In spite of the rapid development of novel transfection materials and methods, the influence of morphology-dependent nanomechanics of malignant osteosarcoma on gene transfection is still unsettled. In this study, cell spreading and adhesion area was adjusted by the prepared micropatterns to regulate focal adhesion (FA) formation and cytoskeletal organization in osteosarcoma cells. The micropattern-dependent FA and cytoskeleton could induce different cellular nanomechanics to affect cell functions. Our results indicated that transfection efficiency was improved with enlarging FA area and cell nanomechanics in micropatterned osteosarcoma. The difference of gene transfection in micropatterned cells was vigorously supported by cellular internalization capacity, Ki67 proliferation ability and YAP mechanotranduction through the regulation of focal adhesion and cytoskeletal mechanics. This study is an attempt to disclose the relationship of cell nanomechanics and gene transfection for efficient gene delivery and develop multifunctional nanomedicine biomaterials for accurate gene therapy in osteosarcoma cells.
研究领域:
生物医学工程
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分子生物学
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癌症研究
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纳米医学
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产品关联
DOI
PubMed
高影响因子
TOXICOLOGY AND APPLIED PHARMACOLOGY
·
2025
·
IF 3.4
Ling-Zi Xia,Jun-Zhe Yue,Li-Jun Wu,Qian-Ying Jin,Yi-Pei Yang,Jing-Yang Yu,Rui-Zhe Pan,Xin Zhang,Xiao-Ying Wu,Jiayin Zhu,Hai-Tao Gao
Phthalates (PEs) are widespread in environment, and human beings are unavoidably exposing to the mixture of PEs, which may induce male reproductive health risks. In order to investigate the mechanism of male reproductive injuries caused by the mixture of di-2-ethylhexyl phthalate, dibutyl phthalate and butyl benzyl phthalate (MPEs), male rats were orally exposed to 16 mg/kg/d MPEs (L-MPEs) and 450 mg/kg/d MPEs (H-MPEs) for 90 days, and the results showed that MPEs decreased the weights of testes, epididymis and periepididymis fat, decreased serum levels of male hormones, increased abnormal sperm rate, and caused testicular histopathological damages, such as atrophy and cavitation of seminiferous tubules, spermatids exfoliation, Leydig cells hyperplasia and accumulation of lipid droplets in the testicular interstitium. Testicular transcriptomic analysis identified 100 differently expressed genes (DEGs) in L-MPEs group and 10,880 DEGs in H-MPEs group, and these DEGs mainly involved in signaling pathways of focal adhesion, PI3K-Akt, AGE-RAGE, axon guidance, PPAR, MAPK and etc. Testicular Paxillin and vinculin were significantly upregulated in MPEs treated groups, initially verified that focal adhesion was a pathway of male reproductive injuries induced by MPEs. This study provides new ideas for the further researches on the mechanism of MPEs' male reproductive toxicity.
研究领域:
毒理学
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分子生物学
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生殖生物学
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环境健康
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基因组学
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产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2022
·Vol. 11
·期 1
·99-108
·
IF 7.571
Yongtao Wang,Nana Wang,Yazhou Chen,Yingjun Yang
Breast cancer is considered as a worldwide disease due to its high incidence and malignant metastasis. Although numerous techniques have been developed well to conduct breast cancer therapy, the influence of micropattern-induced interfacial heterogeneity on the molecular mechanism and nuclear signalling transduction of carcinogenesis is rarely announced. In this study, PDMS stencil-assisted micropatterns were fabricated on tissue culture plates to manage cell clustering colony by adjusting initial cell seeding density and the size of microholes. The curvature of each microholes was controlled to construct the interfacial heterogeneity of MDA-MB231 cancer cells at the periphery of micropatterned colony. The distinguished focal adhesion (FA) and cytoskeleton distribution at the central and peripheral regions of the cell colony were regulated by heterogeneous properties. The interfacial heterogeneity of FA and cytoskeleton would induce the biased tension force to encourage more ezrin expression at the periphery and further promote DNA synthesis, therefore disclosing a stem-like phenotype in heterogeneous cells. This study will provide a value source of information for the development of micropattern-induced heterogeneity and the interpretation of metastatic mechanism in malignant breast cancer cells.
研究领域:
癌症生物学
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细胞生物学
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生物医学工程
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Bioengineering and Biotechnology
·
2020
·
IF 3.644
Lin Ji,Li Xiaokeng,Yin Jun,Qian Jin
The directional alignment and outgrowth of neurons is a critical step of nerve regeneration and functional recovery of nerve systems, where neurons are exposed to a complex mechanical environment with subcellular structures such as stress fibers and focal adhesions acting as the key mechanical transducer. In this paper, we investigate the effects of cyclic stretch on neuron reorientation and axon outgrowth with a feasible stretching device that controls stretching amplitude and frequency. Statistical results indicate an evident frequency and amplitude dependence of neuron reorientation, that is, neurons tend to align away from stretch direction when stretching amplitude and frequency are large enough. On the other hand, axon elongation under cyclic stretch is very close to the reference case where neurons are not stretched. A mechanochemical framework is proposed by connecting the evolution of cellular configuration to the microscopic dynamics of subcellular structures, including stress fiber, focal adhesion, and microtubule, yielding theoretical predictions that are consistent with the experimental observations. The theoretical work provides an explanation of the neuron’s mechanical response to cyclic stretch, suggesting that the contraction force generated by stress fiber plays an essential role in both neuron reorientation and axon elongation. This combined experimental and theoretical study on stretch-induced neuron reorientation may have potential applications in neurodevelopment and neuron regeneration.
研究领域:
神经科学
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生物力学
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细胞生物学
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组织工程
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产品关联
DOI
PubMed
高影响因子
LAB ON A CHIP
·
2015
·Vol. 15
·期 17
·3481-3494
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IF 6.115
Hui Zhao,Lyu Zhou,Qiang Zhang,Xiaoying Zhou,Yonghui Zhang,Huijun Chen,Yanan Du
Phenotypic screening has regained momentum in the pharmaceutical industry owing to its success over target-based screening. Most phenotypic screening relies on nonspecific biochemical readouts regarding cellular viability, which hampers the discovery of novel drug mechanisms of action (MOAs). Here we present a Contractility-based bi-Content micro-Collagen Chip (3CChip), which establishes cellular contractility as a biomechanics-related phenotype for drug screening. Bi-content analysis of cell contractility (imaged by iPhone) and viability suggests that the label-free contractility-based analysis exhibits superior sensitivity to compounds targeting contractile elements (e.g. focal adhesion, cytoskeleton), resulting in a enlarged target pool for drug assessment. Six typical readout patterns of drug response are summarized according to the relative positions of the contraction/viability curves, and drug targets are profiled into three categories (biomechanical, biochemical and housekeeping) by 3CChip, which will benefit subsequent target identification. The simple-to-use and effective 3CChip offers a robust platform for micro-tissue-based functional screening and may lead to a new era of mechanism-informed phenotypic drug discovery.
研究领域:
药学
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生物医学工程
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细胞生物学
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药物发现
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产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2024
·
IF 6.1
Yingjun Yang,Kuankuan Han,Siyuan Huang,Kai Wang,Yuchen Wang,Shukai Ding,Le Zhang,Miao Zhang,Bingshe Xu,Shufang Ma,Yongtao Wang,Shengli Wu,Xinlong Wang
Over the past decades, the critical role of cellular contractility associated mechanotransduction in the regulation of cell functions has been revealed. In this case, numerous biomaterials have been chemically or structurally designed to manipulate cell behaviors through the regulation of cellular contractility. In particular, adhesive proteins including fibronectin, poly-l-lysine and collagen type I have been widely applied in various biomaterials to improve cell adhesion. Therefore, clarifying the effects of adhesive proteins on cellular contractility has been valuable for the development of biomaterials design. In this study, a reference-free traction force microscopy with a well-organized microdots array was designed and prepared to investigate the relationship between adhesive proteins, cellular contractility, and mechanotransduction. The results showed that fibronectin and collagen type I were able to promote the assembly of focal adhesions and further enhance cellular contraction and YAP activity. In contrast, although the poly-l-lysine supported cell spreading and elongation, it was inefficient in inducting cell contractility and activating YAP. Additionally, compared with cellular morphogenesis, cellular contraction was essential for YAP activation.
研究领域:
细胞生物学
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生物物理学
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生物材料科学
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机械生物学
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产品关联
DOI
PubMed
高影响因子
Signal Transduction and Targeted Therapy
·
2025
·Vol. 10
·期 1
·395
·
IF 52.7
Liu Yue,Wang Huirui,Zhan Jie,Sun Jiabo,Sun Yan,Fu Xiaojie,Lv Dongxue,Li Xiuyun,Dong Ting,Lou Hongxiang
The widespread clinical application of paclitaxel (PTX) in cancer treatment has been significantly limited by the emergence of drug resistance and the presence of drug-tolerant persister cells. To systematically identify key regulators of this resistance, we conducted a genome-wide CRISPR/Cas9 knockout screen, which revealed that cell division cycle 6 (CDC6) is a critical determinant of cell adhesion-mediated PTX resistance. Furthermore, our results illustrate that CDC6, an essential DNA replication licensing factor, functions through a pathway distinct from previously well-characterized resistance mechanisms. Genetic depletion of CDC6 considerably sensitizes cells, markedly increasing PTX-induced cell death. In addition to its established role in chromosome stability, CDC6 physically interacts with tropomodulin-3 (Tmod3) in the cytoplasmic compartment. This interaction enhances CDC6 protein stability and drives drug resistance phenotypes through the regulation of actin cytoskeleton remodeling and facilitating focal adhesion assembly. In addition, combination treatment with PTX and actin filament inhibitors synergistically enhanced the antitumor efficacy both in vitro and in vivo. Overall, our studies elucidate the mechanisms through which CDC6 functions as a key regulator of PTX resistance and provide a potential therapeutic strategy to increase PTX efficacy through the modulation of the cytoskeletal-adhesion axis.
研究领域:
癌症生物学
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分子肿瘤学
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细胞信号传导
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药物耐药性
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细胞骨架动力学
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产品关联
DOI
PubMed
高影响因子
Journal of Functional Foods
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2020
·
IF 3.701
ShiFa Ruan,ShiJian Xiang,WenFeng Wu,SiWei Cao,QunQun Du,ZhuXian Wang,TingTing Chen,Qun Shen,Li Liu,HuoJi Chen,LiDong Weng,HongXia Zhu,Qiang Liu
We applied a label-free proteomic method to explore the mechanisms of Licorice flavonoid anti-acne effects in rat. Acne model was established in the back of rats as model group (MDL), then treated with licorice flavonoid (LCF), while none treated rats as control groups (CTR). In MDL, 314 differentially expressed proteins (DEPs) and 27 significantly differentially expressed proteins (SDEPs) were identified compared to what was identified in CTR. While in LCF, 359 DEPs and 15 SDEPs were identified in comparison to MDL. Bioinformatics analysis showed that pathways related to metabolism, tight junction, PI3K-Akt signaling, focal adhesion, regulation of actin cytoskeleton, and leukocyte transendothelial migration were activated. The results of proteomics data were validated by qRT-PCR and western blot. Transdermal administration of LCF may exert anti-acne effects by inhibiting PI3K-Akt signaling pathway and mitochondrial activity. Hence, our results elucidated the underlying mechanisms of LCF anti-acne effect.
研究领域:
药理学
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皮肤科
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蛋白质组学
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分子生物学
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产品关联
DOI
高影响因子
ACS Applied Bio Materials
·
2021
·
IF 0
Linzhi Jing,Xiang Wang,Bin Leng,Ningping Zhan,Hang Liu,Shifei Wang,Yuyun Lu,Jie Sun,Dejian Huang
Scaffold-based three-dimensional (3D) cell culture systems have gained increased interest in cell biology, tissue engineering, and drug screening fields as a replacement of two-dimensional (2D) monolayer cell culture and as a way to provide biomimetic extracellular matrix environments. In this study, microscale fibrous scaffolds were fabricated via electrohydrodynamic printing, and nanoscale features were created on the fiber surface by simply leaching gliadin of poly(ε-caprolactone) (PCL)/gliadin composites in ethanol solution. The microstructure of the printed scaffolds could be precisely controlled by printing parameters, and the surface nanotopography of the printed fiber could be tuned by varying the PCL/gliadin ratios. By seeding mouse embryonic fibroblast (NIH/3T3) cells and human nonsmall cell lung cancer (A549) cells on the printed scaffolds, the cellular responses showed that the fiber nanotopography on printed scaffolds efficiently favored cell adhesion, migration, proliferation, and tissue formation. Quantitative analysis of the transcript expression levels of A549 cells seeded on nanoporous scaffolds further revealed the upregulation of integrin-β1, focal adhesion kinase, Ki-67, E-cadherin, and epithelial growth factor receptors over what was observed in the cells grown on the pure PCL scaffold. Furthermore, a significant difference was found in the relevant biomarker expression on the developed scaffolds compared with that in the monolayer culture, demonstrating the potential of cancer cell-seeded scaffolds as 3D in vitro tumor models for cancer research and drug screening.
研究领域:
组织工程
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细胞生物学
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癌症研究
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药物筛选
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产品关联
DOI
PubMed
Nanoscale
·
2014
·Vol. 6
·期 12
·6959-6969
·
IF 6.739
Zhonglin Lyu,Hongwei Wang,Yanyun Wang,Kaiguo Ding,Huan Liu,Lin Yuan,Xiujuan Shi,Mengmeng Wang,Yanwei Wang,Hong Chen
Efficient control of the self-renewal and pluripotency maintenance of embryonic stem cell (ESC) is a prerequisite for translating stem cell technologies to clinical applications. Surface topography is one of the most important factors that regulates cell behaviors. In the present study, micro/nano topographical structures composed of a gold nanoparticle layer (GNPL) with nano-, sub-micro-, and microscale surface roughnesses were used to study the roles of these structures in regulating the behaviors of mouse ESCs (mESCs) under feeder-free conditions. The distinctive results from Oct-4 immunofluorescence staining and quantitative real-time polymerase chain reaction (qPCR) demonstrate that nanoscale and low sub-microscale surface roughnesses (Rq less than 392 nm) are conducive to the long-term maintenance of mESC pluripotency, while high sub-microscale and microscale surface roughnesses (Rq greater than 573 nm) result in a significant loss of mESC pluripotency and a faster undirectional differentiation, particularly in long-term culture. Moreover, the likely signalling cascades engaged in the topological sensing of mESCs were investigated and their role in affecting the maintenance of the long-term cell pluripotency was discussed by analyzing the expression of proteins related to E-cadherin mediated cell–cell adhesions and integrin-mediated focal adhesions (FAs). Additionally, the conclusions from MTT, cell morphology staining and alkaline phosphatase (ALP) activity assays show that the surface roughness can provide a potent regulatory signal for various mESC behaviors, including cell attachment, proliferation and osteoinduction.
研究领域:
干细胞生物学
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纳米技术
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细胞工程
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生物材料科学
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产品关联
DOI
PubMed
高影响因子
Engineering
·
2024
·
IF 10.1
Peng Wang,Liping Qian,Huixin Liang,Jianhao Huang,Jing Jin,Chunmei Xie,Bin Xue,Jiancheng Lai,Yibo Zhang,Lifeng Jiang,Lan Li,Qing Jiang
Hydrogel-based tissue-engineered skin has attracted increased attention due to its potential to restore the structural integrity and functionality of skin. However, the mechanical properties of hydrogel scaffolds and natural skin are substantially different. Here, we developed a polyvinyl alcohol (PVA)/acrylamide based interpenetrating network (IPN) hydrogel that was surface modified with polydopamine (PDA) and termed Dopa-gel. The Dopa-gel exhibited mechanical properties similar to native skin tissue and a superior ability to modulate paracrine functions. Furthermore, a tough scaffold with tensile resistance was fabricated using this hydrogel by three-dimensional printing. The results showed that the interpenetration of PVA, alginate, and polyacrylamide networks notably enhanced the mechanical properties of the hydrogel. Surface modification with PDA endowed the neat hydrogels with increased secretion of immunomodulatory and proangiogenic factors. In an in vivo model, Dopa-gel treatment accelerated wound closure, increased vascularization, and promoted a shift in macrophages from a proinflammatory M1 phenotype to a prohealing and anti-inflammatory M2 phenotype within the wound area. Mechanistically, the focal adhesion kinase (FAK)/extracellular signal-related kinase (ERK) signaling pathway may mediate the promotion of skin defect healing by increasing paracrine secretion via the Dopa-gel. Additionally, proangiogenic factors can be induced through Rho-associated kinase-2 (ROCK-2)/vascular endothelial growth factor (VEGF)-mediated paracrine secretion under tensile stress conditions. Taken together, these findings suggest that the multifunctional Dopa-gel, which has good mechanical properties similar to those of native skin tissue and enhanced immunomodulatory and angiogenic properties, is a promising scaffold for skin tissue regeneration.
研究领域:
组织工程
·
生物医学材料
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伤口愈合
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生物材料科学
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产品关联
DOI
高影响因子
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
·
2017
·
IF 4.521
Jing Zhang,Li Li,Yueting Peng,Yu Chen,Xiaoying Lv,Shun Li,Xiang Qin,Hong Yang,Chunhui Wu,Yiyao Liu
Tumor cell can be significantly influenced by various chemical groups of the extracellular matrix proteins. However, the underlying molecular mechanisms involved in the interaction between cancer cells and functional groups in the extracellular matrix remain unknown. Using chemically modified surfaces with biological functional groups (CH 3 , NH 2 , OH), it was found that hydrophobic surfaces modified with CH 3 and NH 2 suppressed cell proliferation and induced the number of apoptotic cells. Mitochondrial dysfunction, cytochrome c release, Bax upregulation, cleaved caspase-3 and PARP, and Bcl-2 downregulation indicated that hydrophobic surfaces with CH 3 and NH 2 triggered the activation of intrinsic apoptotic signaling pathway. Cells on the CH 3 - and NH 2 -modified hydrophobic surfaces showed downregulated expression and activation of integrin β1, with a subsequent decrease of focal adhesion kinase (FAK) activity. The RhoA/ROCK/PTEN signaling was then activated to inhibit the phosphorylation of PI3K and AKT, which are essential for cell proliferation. However, pretreatment of MDA-MB-231 cells with SF1670, a PTEN inhibitor, abolished the hydrophobic surface-induced activation of the intrinsic pathway. Taken together, the present results indicate that CH 3 - and NH 2 -modified hydrophobic surfaces induce mitochondria-mediated apoptosis by suppressing the PTEN/PI3K/AKT pathway, but not OH surfaces. These findings are helpful to understand the interaction between extracellular matrix and cancer cells, which might provide new insights into the mechanism potential intervention strategies for tumor prognosis.
研究领域:
癌症生物学
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细胞生物学
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分子生物学
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生物化学
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）