LANGMUIR
·
2024
·
IF 3.7
Xiaokai Pan,Juan Nie,Jiacheng Lei,Peng Wang,Kaikai Zheng,Qiang Wei,Xiaojing Liu
Understanding how the spatial distribution of adhesive ligands regulates cell behavior is crucial for designing biomaterials. This study investigates how precisely controlled ligand spacing affects cell spreading and integrin subtype engagement. Using engineered polyacrylamide hydrogels with gold nanoparticle arrays, we explored the impact of RGD ligand spacings (30 and 150 nm) on human mesenchymal stromal cells. Cells exhibited distinct morphological behaviors: smaller spacings promoted larger spreading areas, while larger spacings resulted in elongated shapes with reduced spreading. Mechanistically, we found that the α5β1 integrin, not the αvβ3 integrin, played a central role in mediating these responses, alongside lamellipodia formation. Our findings provide critical insights into the spatial sensing of ligands, highlighting the influence of ligand spacing on cellular mechanotransduction and integrin-specific responses. This work advances the understanding of cell-material interactions and offers potential strategies for designing biomaterials to guide cell behavior in tissue engineering.
研究领域:
细胞生物学
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生物材料科学
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组织工程
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生物物理学
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产品关联
DOI
PubMed
高影响因子
iScience
·
2024
·
IF 4.6
Zijia Chen,Xiaoning Han,Bo Che,Huiping Feng,Yue Zhou,Linhong Deng,Xiang Wang
Soft tissues experience strain under mechanical stresses, storing energy as residual stresses and strain energy. However, the specific impact of such strain on cell migration and its molecular mechanisms remains unclear. In this study, we investigated this by using polydimethylsiloxane (PDMS) membranes with varying prestrain levels but constant stiffness to mimic tissue-like conditions. Results showed that higher prestrain levels enhanced 3T3 fibroblast adhesion and reduced filopodia formation. Elevated prestrain also increased integrin and vinculin expression, which was associated with lower cell migration rates. Notably, both 3T3 fibroblasts and primary rat airway smooth muscle cells migrated faster toward higher prestrain areas on substrates with strain gradients. Knockdown of integrin or vinculin inhibited 3T3 cell migration directionality, highlighting their critical role. This research reveals a mechanobiological pathway where strain gradients direct cell migration, providing insight into a common mechanotransduction pathway influencing cellular responses to both stiffness and strain-related mechanical cues.
研究领域:
细胞生物学
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生物力学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Today Bio
·
2024
·
IF 8.7
Wenli Jiang,Xinghong Yao,Jian Zhong,Zhi Ouyang,Junyi Shen,Yan Qiu,Ye Zeng
The mechanical environment of vascular endothelial cells (ECs) encompasses a wide range of curvatures due to variations in blood vessel diameters. Integrins, key mediators of cell-matrix interactions, establish connections between the extracellular matrix and the actin cytoskeleton, influencing diverse cellular behaviors. In this study, we explored the impact of spatial confinement on human umbilical vein ECs (HUVECs) cultured within three-dimensional hydrogel microgrooves of varying curvatures and the underlying role of integrins in mediating cellular responses. Employing maskless lithography, we successfully fabricated precise and wall curvatures-controlled hydrogel microgrooves, conferring spatial constraints on the cells. Our investigations revealed substantial alterations in HUVEC behavior within the hydrogel microgrooves with varying sidewall curvatures, marked by reduced cell size, enhanced orientation, and increased apoptosis. Interestingly, microgroove curvature emerged as a crucial factor influencing cell orientation and apoptosis, with rectangular microgrooves eliciting distinct changes in cell orientation, while ring-form microgrooves exhibited higher apoptosis rates. The side-wall effect in the 20 μm region near the microgroove wall had the greatest influence on cell orientation and apoptosis. HUVECs within the microgrooves exhibited elevated integrin expression, and inhibition of αV-integrin by cilengitide significantly curtailed cell apoptosis without affecting proliferation. Additionally, integrin-mediated cell traction force closely correlated with the spatial confinement effect. Cilengitide not only reduced integrin and focal adhesion expression but also attenuated cell traction force and cytoskeletal actin filament alignment. Overall, our findings elucidate the spatial confinement of ECs in hydrogel microgrooves and underscores the pivotal role of integrins, particularly αV-integrin, in mediating cell traction force and apoptosis within this microenvironment.
研究领域:
生物力学
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细胞生物学
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血管生物学
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产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2015
·Vol. 5
·期 112
·92292-92302
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IF 3.84
Meng Cai,Mengyuan Ye,Xingxing Shang,Honghao Sun,Mingxing Liu,Hongmei Sun,Zhuo Ma,Hongda Zhu
Polymeric micelles as nanocarrier-based drug delivery systems provide an innovative platform for selectively delivering active molecules and offer better antitumour activity. However, circulation stability in vivo, controllable drug intracellular release and high targeting efficiency are several practical challenges for micelles. Therefore, we developed cRGD-modified and shell crosslinked micelles (RSCMs) based on amphiphilic poly(styrene-co-maleic anhydride) (SMA). RSCMs exhibited a spherical shape and were homogeneous with an average diameter of 106.1 nm and a low polydispersity of 0.087. In comparison, after crosslinking the micelles possessed better stability against dilution and stronger redox-response towards dithiothreitol (DTT). The SMA micelles displayed high drug loading capacity for hydrophobic DOX with a drug loading of approximately 14.1–19.2% (w/w) and an encapsulation efficiency of 72.1–82.7% (w/w). The in vitro release studies of shell crosslinked micelles showed that DOX release was minimal (<25%, 24 h) under physiological conditions. However, in the presence of 10 mM DTT, accelerated release of DOX was achieved (60%, 24 h). MTT assays in B16F10 cells indicated that RSCMs displayed low cytotoxicity up to a concentration of 500 μg ml−1. Moreover, the IC50 value showed that cRGD-DOX-ss-M could be more effective than other groups. In vitro, cellular uptake was further studied with confocal laser scanning microscopy and flow cytometry, both the qualitative and quantitative results demonstrated that cRGD-DOX-ss-M possessed much better specificity to cancer cells and superior stimulated release property in cytoplasm. Notably, cRGD-DOX-ss-M could more efficiently be delivered to and release into the nuclei of αvβ3 integrin over expressing tumor cell line (B16F10) than counterparts of integrin-deficient tumor cells (Hela). Thus, these cRGD-modified redox-sensitive micelles have appeared as a technology platform with great potential for targeted anticancer drug delivery and release for integrin over expressing tumor cells.
研究领域:
药剂学
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肿瘤学
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纳米医学
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产品关联
DOI
高影响因子
RSC Advances
·
2014
·Vol. 4
·期 16
·8191-8199
·
IF 3.708
Haiyan Chen,Min Zhang,Haibo Yang,Weixia Xu,Yuxiang Ma,Yueqing Gu
The unique properties of gold nanoclusters (Au NCs) enable them to be functionalized as fluorescent probes or pro-drugs for biomedical application. A facile approach was introduced to synthesize nanoconjugates (Au–cRGD–MPA), which was composed of Au NCs, cyclic (Arg–Gly–Asp–DTyr–Lys) (cRGD) peptide and a near infrared (NIR) fluorescence dye (MPA). The nanoconjugates exhibited dual fluorescence in the visible range and NIR range simultaneously. The low cytotoxicity of Au–cRGD–MPA was demonstrated in MCF-7 cell line and U87 cell line. The cell affinity investigations verified the outstanding tumor-targeting capability of Au–cRGD–MPA for tumor cells. The biodistribution characteristics and tumor targeting ability of the probes were elucidated in normal nude mice and tumor-bearing mice, respectively. Attributing to the small size (less than 5 nm), the majority of the nanoconjugates metabolized from the living subjects via the kidney-bladder pathway. Additionally, Au–cRGD–MPA displayed favorable tumor-specificity in Integrin αvβ3 over-expressed tumor-bearing (MDA-MB-231) mice. Consequently, the results demonstrated that the dual fluorescence probe is a promising candidate for tumor imaging and disease treatment monitoring.
研究领域:
生物医学工程
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分子影像学
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纳米医学
✓ 已验证
产品关联
DOI
高影响因子
Journal of Nanomaterials
·
2016
·
IF 1.758
Xiaochao Qu,Xiaoxiao Li,Jingning Liang,Yanran Wang,Muhan Liu,Jimin Liang
Gold nanomaterials as computed tomography (CT) contrast agents at lower X-ray dosage to get a higher contrast have advantages of longer imaging time and lower toxic side effects compared to current contrast agents. As a receptor for Cyclo (Arg-Gly-Asp-D-Phe-Lys) (RGD) peptide, integrin is overexpressed on some tumor cells and tumor neovasculature. In this paper, we conjugated the RGD peptide on the surface of gold nanorods (AuNRs), designated as RGD-AuNRs, a promising candidate in applications such as tumor targeting and imaging capability for micro-CT imaging. Integrin -positive U87 cells and integrin -negative HT-29 cells were chosen to establish animal models relatedly and then texted the tumor targeting ability and imaging capability of RGD-AuNRs in vitro and in vivo. The MTT assay and stability measurement showed that RGD-conjugation eliminated their cytotoxicity and improved their biocompatibility and stability. Dark-field imaging of U87 cells and HT-29 cells testified the binding affinities and uptake abilities of RGD-AuNRs, and the results showed that RGD-AuNRs were more specifical to U87 cells. The enhanced micro-CT imaging contrast of intramuscular and subcutaneous injection illustrated the feasibility of RGD-AuNRs to be contrast agents. Furthermore, the micro-CT imaging of targeting U87 and HT-29 tumor models verified the targeting abilities of RGD-AuNRs.
研究领域:
医学影像学
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纳米生物学
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肿瘤学
✓ 已验证
产品关联
DOI
高影响因子
CELL CYCLE
·
2021
·
IF 4.534
Limei Yan,Zeping He,Wei Li,Ning Liu,Song Gao
Rhophilin Rho GTPase binding protein 2 (P76RBE) belongs to rhophilin family of Rho-GTPase-binding proteins and is found to contribute to the development of diverse cancers. Data in Oncomine and Kaplan–Meier Plotter databases showed that P76RBE was upregulated in ovarian cancer tissues compared with normal tissues, and patients with high P76RBE expression had worse overall survival, which indicated P76RBE may be associated with the pathogenesis of ovarian cancer. This study aimed to investigate the role of P76RBE in ovarian cancer and to reveal the possible underlying mechanisms. The results demonstrated that P76RBE was highly expressed in ovarian cancer tissues and ovarian cancer cell lines. Functionally, silencing of P76RBE suppressed the proliferation, induced cell cycle arrest, and inhibited migration and invasion in OVCAR-3 and OV-90 cells, while overexpression of P76RBE showed opposite effects on A2780 cells. Mechanically, P76RBE silencing resulted in downregulation of integrin β1, accompanying the reduced NF-κB p65 phosphorylation and nuclear translocation. Importantly, integrin β1 knockdown effectively rescued the effects of P76RBE overexpression on ovarian cancer cells with suppressed proliferation, migration, and invasion. Additionally, in the xenograft tumors derived from OVCAR-3 and OV-90 cell lines, P76RBE knockdown inhibited tumor growth. Meanwhile, the expression of integrin β1 and NF-κB p65 phosphorylation was decreased. In summary, our findings indicate that P76RBE contributes to the progression of ovarian cancer through regulating the integrin β1/NF-κB signaling, and it may be a promising target for ovarian cancer therapy.
研究领域:
肿瘤学
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分子生物学
·
细胞生物学
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产品关联
DOI
PubMed
高影响因子
BMC CANCER
·
2022
·Vol. 22
·期 1
·1-12
·
IF 4.638
Chen Xueqin,Wang Yan,Liu Hancong,Zhang Jingjing,Wang Jie,Jin Xiaobao,Ma Yan
Background In our previous study, N end of the Circumsporozoite protein (CSP I-plus) modified recombinant human Endostatin (rEndostatin, endostar) (rES-CSP) was constructed, which had antiangiogenic capability and bound to hepatocellular carcinoma in vivo and in vitro. In this study, the inhibition of rES-CSP on hepatocellular carcinoma metastasis was verified in vivo and in vitro, and its possible mechanism was explored. Methods Firstly, the impact of rES-CSP on the migration, adhesion of hepatoma cell HCCLM3 was identified by wound healing, transwell, and on metastasis of orthotopic xenograft model was identified in nude mouse. Then the expression of metastasis-associated molecules (MMP2, E-cadherin, integrinβ1) and angiogenesis-related factors (VEGFA) in vitro and in vivo were detected by real-time PCR, western blotting, immunohistochemistry. Results Finally, we found that rES-CSP could inhibit the migration and invasion of HCCLM3, and decrease tumor metastasis and growth in nude mouse orthotopic xenograft models. The tumor inhibiting rates of rES-CSP and Endostar were 42.46 ± 5.39% and 11.1 ± 1.88%. The lung metastasis rates of the control, Endostar and rES-CSP were 71, 50, and 42.8%, respectively. Compared with Endostar, rES-CSP significantly down-regulated the expression of VEGFA and integrinβ1. Heparin, a competitive inhibitor of CSP I-plus, which can be bind to the highly-sulfated heparan sulfate proteoglycans (HSPGs) over-expressed in liver and hepatocellular carcinoma, alleviated the down-regulation of VEGFA and integrinβ1. Conclusions These indicate that rES-CSP may play a role in inhibiting tumor growth and metastasis by down-regulating the angiogenic factor VEGF and the metastasis-related molecules or by interfering with HSPGs-mediated tumor metastasis.
研究领域:
肿瘤学
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分子生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOLOGY OF REPRODUCTION
·
2025
·
IF 3
Zhang Yingying,Zhang Eryun,Li Ling,Ren Yongwei,Zhang Jinqiu,Zheng Qiutong,Sun Minya,Zhao Shaojie,Cui Yugui,Gu Ying,Xu Zhice
The risk of multiple placental thrombosis is significantly elevated in preeclampsia, and the vascular endothelium plays a vital role in coagulation processes through the secretion of Integrin alpha 2b, von Willebrand factor, and tissue factor. However, the underlying pathological mechanisms remain unclear. In this study, placental blood vessels were collected from both preeclampsia and normal pregnancies. Protein levels of Integrin alpha 2b were found to be up-regulated in preeclampsia samples compared to controls, indicating enhanced coagulation function in preeclampsia placental tissue. Additionally, higher cholesterol levels of plasma and lower AlkB homolog 1 expression in placental blood vessels of preeclampsia were found, overall DNA N6-methyldeoxyadenosine levels were up-regulated. Interestingly, the DNA N6-methyldeoxyadenosine level at the Integrin alpha 2b promoter was decreased. Cholesterol overload experiments in human umbilical vein endothelial cells demonstrated that cholesterol regulates the protein expression of AlkB homolog 1 and Integrin alpha 2b in a concentration-dependent manner. Furthermore, Integrin alpha 2b protein expression was increased following AlkB homolog 1 knockout, but no changes were observed when cholesterol was incubated with AlkB homolog 1 knockout cells. These findings provide critical insights into the roles of cholesterol levels, AlkB homolog 1, and Integrin alpha 2b in coagulation function within placental blood vessels. This information may contribute to further investigations of potential therapeutic targets and early prevention strategies for placental thrombosis in preeclampsia.
研究领域:
医学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2018
·
IF 4.556
Shihong Shao,Yun Zhu,Tingting Meng,Yupeng Liu,Yun Hong,Ming Yuan,Hong Yuan,Fuqiang Hu
Liver metastasis is a leading death cause in colorectal cancer. The pathological differences between orthotopic tumors and metastatic lesions increased the therapeutic difficulty of metastasis. Herein, the α5β1 integrin receptor expression on metastatic cells was first measured, the result showed that metastatic cells expressed the α5β1 integrin higher than that of the original cells from orthotopic tumors. Afterward, RPM peptide-modified chitosan-stearic (RPM-CSOSA) was designed based on α5β1 integrin expression. The cytotoxicity and resistance to migration and the invasion ability of the targeting drug delivery system loading doxorubicin (DOX) and curcumin (CUR) were evaluated in vitro. The metastatic inhibition of the targeting drug delivery system was also investigated in HT29 liver metastatic models. The modified RPM peptide could increase the cellular internalization of CSOSA micelles in metastatic tumor cells and endothelial cells mediated by α5β1 integrin. The synergistic effects of RPM-CSOSA/DOX and RPM-CSOSA/CUR could obviously inhibit migratory and invasive abilities of HT29 cells and endothelial cells. Moreover, the RPM-CSOSA/DOX&RPM-CSOSA/CUR could obviously decrease the number of metastatic sites by 86.96%, while CSOSA/DOX&CSOSA/CUR decreased liver metastasis by 66.58% compared with that in the saline group. In conclusion, the RPM peptide-modified drug delivery system may provide insights into targeting the metastatic cells overexpressing the α5β1 integrin, and it has the potential to inhibit liver metastasis of colorectal cancer.
研究领域:
肿瘤学
·
药剂学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2022
·
IF 5.364
Weihao Liu,Huan Ma,Ranxi Liang,Xijian Chen,Hongyan Li,Tu Lan,Jijun Yang,Jiali Liao,Zhi Qin,Yuanyou Yang,Ning Liu,Feize Li
Targeted radionuclide therapy based on α-emitters plays an increasingly important role in cancer treatment. In this study, we proposed to apply a heterodimeric peptide (iRGD-C6-lys-C6-DA7R) targeting both VEGFR and integrins as a new vector for 211At radiolabeling to obtain high-performance radiopharmaceuticals with potential in targeted alpha therapy (TAT). An astatinated peptide, iRGD-C6-lys(211At-ATE)-C6-DA7R, was prepared with a radiochemical yield of ∼45% and high radiochemical purity of >95% via an electrophilic radioastatodestannylation reaction. iRGD-C6-lys(211At-ATE)-C6-DA7R showed good stability in vitro and high binding ability to U87MG (glioma) cells. Systematic in vitro antitumor investigations involving cytotoxicity, apoptosis, distribution of the cell cycle, and reactive oxygen species (ROS) clearly demonstrated that 211At-labeled heterodimeric peptides could significantly inhibit cell viability, induce cell apoptosis, arrest the cell cycle in G2/M phase, and increase intracellular ROS levels in a dose-dependent manner. Biodistribution revealed that iRGD-C6-lys(211At-ATE)-C6-DA7R had rapid tumor accumulation and fast normal tissue/organ clearance, which was mainly excreted through the kidneys. Moreover, in vivo therapeutic evaluation indicated that iRGD-C6-lys(211At-ATE)-C6-DA7R was able to obviously inhibit tumor growth and prolong the survival of mice bearing glioma xenografts without notable toxicity to normal organs. All these results suggest that TAT mediated by iRGD-C6-lys(211At-ATE)-C6-DA7R can provide an effective and promising strategy for the treatment of glioma and some other tumors.
研究领域:
放射性药物
·
肿瘤学
·
分子影像
✓ 已验证
DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2025
·
IF 5.6
Feng Li,Xinrong Fan,Bohao Wang,Jingyang Tong,Menglai Ling,Haibin Tong,Yumei Huang
Acute lung injury (ALI) in neonates presents a grave threat to infant health, characterized by a heightened risk of mortality. Phillyrin, an extraordinary constituent derived from a traditional Chinese medicinal herb Forsythia suspensa , has garnered considerable attention for its pronounced anti-inflammatory properties. However, its therapeutic potential for acute inflammatory diseases in neonates remains unclear. Therefore, our current study endeavors to assess the protective effects of phillyrin against lipopolysaccharide (LPS)-induced ALI in neonates and elucidate the underlying mechanisms. Phillyrin exhibited significant amelioration of lung damage in neonatal rats with LPS-induced ALI, accompanied by reductions in the total cell counts, neutrophil counts, and total protein level in bronchoalveolar lavage fluid (BALF). Notably, phillyrin substantially attenuated proinflammatory cytokine secretion and suppressed NF-κB activation in the lungs of neonatal ALI rats; however, it demonstrated inefficacy in mitigating LPS-induced cytokine secretion and NF-κB activation in vitro . Notably, phillyrin effectively inhibited β2 integrin-mediated neutrophil adhesion, migration, and chemotaxis. Moreover, phillyrin robustly suppressed β2 integrin engagement-induced actin polymerization and the Vav1/Rac1/PAK1/LIMK1/cofilin pathway. From a mechanistic standpoint, phillyrin exhibited direct interaction with β2 integrin, effectively antagonizing its function and significantly disrupting its binding affinity to intercellular adhesion molecule 1 (ICAM-1). This investigation unveils the promising therapeutic prospects of phillyrin as a novel compound against neonatal ALI.
研究领域:
药理学
·
免疫学
·
呼吸病学
✓ 已验证
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）