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ACS Applied Materials & Interfaces · 2025 · IF 8.2

Nuclear Deformation and Stiffness-Dependent Traction Force Generation Dictate the Migration of Cells under Confinement

Zheng Wang,Feng Xu,Di Wu,Wei Huang,Zhiqin Chu,Yuan Lin

Cells need to migrate through confined spaces during processes such as embryo development and cancer metastasis. However, the fundamental question of how confinement size and surrounding rigidity collectively regulate the migration capability of cells remains unclear. Here, by utilizing maskless photolithography with a digital micromirror device (DMD), a microchannel with precisely controlled width and wall stiffness (similar to those exhibited by natural tissues) is fabricated. We find that increasing the rigidity of the confining wall leads to a more reduced nuclear volume but has no detectable influence on the myosin expression level in the cells. More interestingly, a biphasic trend of the cell speed is observed, with the migration velocity reaching its minimum at an intermediate wall rigidity of ∼10 kPa. A motor-clutch-based pulling race model is then proposed, which suggests that such biphasic dependence is due to the fact that a very soft channel wall will result in small deformation of the nucleus and consequently reduced cell-wall friction, while larger myosin-based crawling force can be triggered by a stiff confining boundary, both leading to a relatively high migration speed. These findings could provide critical insights into novel strategies for controlling the movement of cells and the design of high-performance biological materials.

研究领域: 细胞生物学 · 生物力学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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CARBOHYDRATE POLYMERS · 2025 · IF 12.5

Isolation and structural identification of the homogeneous polysaccharide CGPA1 from Calvatia gigantea with wound healing effects

Xiuhua Meng,Wenjian Zhao,Yanan Zhao,Juntong Guo,Xiaoqin Ding,Yanan Gai,Han Lv,Yiwei Wang,Jian Chen

Calvatia gigantea is a traditional Chinese medicinal fungus known for its diverse pharmacological effects, with polysaccharides being one of its main bioactive components. In this study, a novel homogeneous water-soluble polysaccharide (CGPA1) was successfully isolated and purified from the fruiting body of Calvatia gigantea . The molecular weight of CGPA1 was determined to be 11.69 kDa. Structural characterization was performed using a combination of high-performance gel permeation chromatography (HPGPC), Fourier-transform infrared spectroscopy (FTIR), methylation analysis, and nuclear magnetic resonance (NMR) spectroscopy. The analysis data revealed that CGPA1 is primarily composed of galactose, methyl-galactose, mannose, xylose, and glucose in a molar ratio of 60.01:27.16:10.34:1.83:0.67. The backbone structure predominantly consists of α-1,6-Gal-(1 → and α-1,6 (3-MeO)-Gal-(1→, with side chains of α-Gal and α-Man. Morphological analysis using SEM, XRD, and AFM, combined with Congo red experiments, suggesting that CGPA1 adopts an amorphous granular chain conformation. Both in vitro and in vivo tests confirmed that CGPA1 can promote the migration of MSF cells and accelerate the healing of acute injured wounds. It was found to facilitate skin re-epithelialization, and collagen deposition over the healing process.

CAS / MDL: 67-68-5 74-88-4
研究领域: 药理学 · 生物化学 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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iScience · 2024 · IF 4.6

Focal adhesion-mediated directional cell migration guided by gradient-stretched substrate

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.

CAS / MDL: 111-30-8
研究领域: 细胞生物学 · 生物力学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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TOHOKU JOURNAL OF EXPERIMENTAL MEDICINE · 2025 · IF 1.6

HOXA1 Promotes Migration, Invasion and Cell Cycle, and Suppresses Cisplatin Sensitivity of Laryngeal Cancer Cells By Mediating AKT/mTOR Pathway

Shaohao Luo,Yunfei Bai,Boqian Wang,Haixia Xu,Shu Zhang,Gang Guo,Xin Li,Hongyang Sun,Xiaobo Cui

Homeobox A1 (HOXA1) is implicated in the progression of various cancers, but its biological function in laryngeal cancer (LC) remains undefined, which is the foothold of our study. Bioinformatics analysis and survival analysis were performed to predict HOXA1 expression in LC tissues, and the prognostic relationship between high HOXA1 expression and LC. Whether high HOXA1 expression correlated with the clinical characteristics and prognosis of LC patients was analyzed. LC cell viability and sensitivity to cisplatin were determined by Methyl thiazolyl tetrazolium assay. The cell migration, invasion, and cell cycle after transfection were examined by Wound healing, Transwell, and flow cytometry assays, respectively. The corresponding mRNA and protein expressions were measured by quantitative real-time PCR or Western blot. A higher expression of HOXA1 was detected in LC tissues, which was found to be relevant to poor prognosis of LC patients. The association of high expression of HOXA1 with lymph node and clinical stage was also confirmed. Silencing of HOXA1 in LC cells enhanced the cell sensitivity to cisplatin, inhibited viability, migration, invasion and cell cycle, and reduced N-Cadherin, Vimentin, PCNA, p-AKT and p-mTOR expressions, while overexpression of HOXA1 had the opposite effects. Collectively, HOXA1 boosts migration, invasion and cell cycle, while suppressing cisplatin sensitivity of LC cells by mediating AKT/mTOR pathway, hinting that HOXA1 is a promising biomarker for diagnosis and prognosis of LC in clinical practice.

CAS / MDL: 30525-89-4 548-62-9
研究领域: 肿瘤学 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Arabian Journal of Chemistry · 2022 · IF 6.212

In vitro wound healing evaluation, antioxidant and chemical profiling of Baeckea frutescens leaves ethanolic extract

Ihsan Safwan Kamarazaman,Nor Azah Mohamad Ali,Fauziah Abdullah,Nazrin Che Saad,Aida Azlina Ali,Salfarina Ramli,Pornchai Rojsitthisak,Hasseri Halim

Occurrence of the wound or chronic wound, which results to disability, amputation and diminish quality of life, are leading to increased healthcare expenditure around the globe. Despite effective conventional wound healing medicines, the exploration of alternative medicines are continuing process as researchers seek for the approach to reduce the cost of wound healing management. In present study, wound healing properties of ethanolic extract of Baeckea frutescens leaves were determined by evaluating their cytotoxicity, proliferation and migration rate on two types of cells, keratinocytes (HaCaT) and fibroblasts (BJ). Furthermore, the antioxidant properties of this plant were determined by DPPH scavenging, ferric reducing antioxidant power (FRAP) and total phenolics content (TPC) assays. The phytochemistry of the extract was evaluated by phytochemicals screening and liquid chromatography mass spectrometry (LCMS) analysis. Results of this study indicated Baeckea frutescens extract increased the rate of proliferation and migration on both HaCat and BJ cells within their nontoxic doses. The extract also possessed a very good antioxidant property as demonstrated with high DPPH radical scavenging, FRAP and TPC values, comparable to that of Green tea extract, a widely known antioxidant. The phytochemistry analyses and LCMS exhibited the presence saponins, flavonoids, tannins and steroids in Baeckea frutescens extract possibly responsible to their antioxidant and wound healing properties.

研究领域: 药理学 · 植物化学
✓ 已验证 DOI 高影响因子
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BIOCONJUGATE CHEMISTRY · 2024 · IF 4

Ratiometric Fluorescence Probes for In Situ Imaging of Membrane Tension in Live Cells

Hai-Yan Wen,Yusi Hu,You-Yang Duo,Liang Zhao,Zhi-Gang Wang,Shu-Lin Liu

Membrane tension is an important physical parameter of describing cellular homeostasis, and it is widely used in the study of cellular processes involving membrane deformation and reorganization, such as cell migration, cell spreading, and cell division. Despite the importance of membrane tension, direct measurement remains difficult. In this work, we developed a ratiometric fluorescent probe sensitive to membrane tension by adjusting the carbon chain structure based on polarity-sensitive fluorophores. The probe is sensitive to changes in membrane tension after cells were subjected to physical or chemical stimuli, such as osmotic shock, lipid peroxidation, and mechanical stress. When the polarity of the plasma membrane increases (the green/red ratio decreases) and the membrane tension increases, the relative magnitude of the membrane tension can be quantitatively calculated by fluorescence ratio imaging. Thus, the probe proved to be an efficient and sensitive membrane tension probe.

研究领域: 细胞生物学 · 生物物理学
✓ 已验证 DOI PubMed 高影响因子
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JOURNAL OF CELLULAR AND MOLECULAR MEDICINE · 2021 ·Vol. 25 ·期 7 ·3361-3370 · IF 5.31

TNFAIP8 regulates gastric cancer growth via mTOR-Akt-ULK1 pathway and autophagy signals

Zheng Chen,Jianguo Zhang,Chenyang Dong,Dongsheng Li,Yuehan Yin,Wenhai Yu,Yuezhi Chen

In this study, the purpose of this study was to investigate the role of TNFAIP8 in gastric cancer (GC). The expression of TNFAIP8 was detected by RT-PCR or western blot . TNFAIP8 was silenced or overexpressed in two cell lines. CCK-8 assay, transwell assay and flow cytometry were used to analyse cell viability, cell invasion capability and apoptosis, respectively. Nude mice were inoculated with TNFAIP8 silencing or overexpressing cells to form transplanted tumours. HE staining and immunohistochemistry assay were performed to assess histopathological changes in tumours. We found that the mRNA and protein expression of TNFAIP8 were significantly up-regulated in GC tumour tissues and cells compared with the normal counterparts. Overexpression of TNFAIP8 in GC cells increased cell viability, decreased apoptosis and promoted the cell migration ability. Meanwhile, increased expression of TNFAIP8 promoted autophagy, while inhibiting mTOR-Akt-ULK1 signal pathway. In conclusions, this study presents data that TNFAIP8 inhibits GC cells presumably by down-regulating mTOR-Akt-ULK1 signal pathway and activating autophagy signal.

CAS / MDL: 55094-52-5
研究领域: 肿瘤学 · 分子生物学 · 细胞生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS · 2023 · IF 3.1

Tunneling nanotube-transmitted mechanical signal and its cellular response

Yan Wang,Xiaoning Han,Linhong Deng,Xiang Wang

Tunneling nanotubes (TNTs) are elastic tubular structures that physically link cells, facilitating the intercellular transfer of organelles, chemical signals, and electrical signals. Despite TNTs serving as a multifunctional pathway for cell-cell communication, the transmission of mechanical signals through TNTs and the response of TNT-connected cells to these forces remain unexplored. In this study, external mechanical forces were applied to induce TNT bending between rat kidney (NRK) cells using micromanipulation . These forces, transmitted via TNTs, induced reduced curvature of the actin cortex and increased membrane tension at the TNT-connected sites. Additionally, TNT bending results in an elevation of intracellular calcium levels in TNT-connected cells, a response attenuated by gadolinium ions, a non-selective mechanosensitive calcium channel blocker . The degree of TNT deflection positively correlated with decreased actin cortex curvature and increased calcium levels. Furthermore, stretching TNT due to the separation of TNT-connected cells resulted in decreased actin cortex curvature and increased intracellular calcium in TNT-connected cells. The levels of these cellular responses depended on the length changes of TNTs. Moreover, TNT connections influence cell migration by regulating cell rotation, which involves the activation of mechanosensitive calcium channels . In conclusion, our study revealed the transmission of mechanical signals through TNTs and the subsequent responses of TNT-connected cells, highlighting a previously unrecognized communication function of TNTs. This research provides valuable insights into the role of TNTs in long-distance intercellular mechanical signaling .

CAS / MDL: 10138-52-0
研究领域: 细胞生物学 · 生物物理学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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MICROCHEMICAL JOURNAL · 2024 · IF 4.9

Wound healing assay on a gravity-driven unidirectional perfusion microfluidic device

Yirong Chen,Yuanyuan Xie,Wen Sun,Ke Ning,Lingke Feng,Xiaoqing Chen,Yan Li,Ling Yu

Cell migration plays a pivotal role in a multitude of physiological and pathological processes, including tissue development, wound healing, immune response, and cancer metastasis. While traditional two-dimensional (2D) cell culture assays, such as the wound healing (scratch) test, have provided valuable insights into cell migration mechanisms, they are unable to replicate the complex in vivo environment. This study introduces a gravity-driven, pump-free microfluidic device to simulate in vivo flow conditions and to investigate the effects of flow rate and flow direction on wound healing assays. The regulation of the flow rate was achieved through adjustments to the tilt angle of the rocking plate. To evaluate the fluid dynamics and cell migration behavior under different flow conditions, numerical simulations and experimental analyses were conducted. The results showed that cell migration and wound healing were markedly influenced by the direction of fluid flow and the magnitude of flow rate. Specifically, compared to the static group, the wound healing rate increased by 76%±6% when the flow direction formed a 45° angle with the wound scratch axis at a -flow rate of 3.0 mL/min, corresponding shear stress of 0.38 dyne/cm 2 . Furthermore, cells exhibited enhanced alignment and migration in the direction of the fluid flow, with the most pronounced effects observed at angles of 45° and 90° between the scratch pattern and the flow direction. Analysis of the cell numbers within the wound healing area and measurements of individual cell area revealed that while the flow conditions did not enhance cell movement, they promoted cell spreading, making the collective wound healing region more pronounced. This gravity-driven, pump-free microfluidic device provides a cost-effective and physiologically relevant platform for studying cell migration, with potential applications in cancer research, wound healing, and developmental biology.

研究领域: 生物工程 · 细胞生物学 · 医学研究
✓ 已验证 DOI 高影响因子
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COLLOIDS AND SURFACES B-BIOINTERFACES · 2016 · IF 3.902

Single cell migration dynamics mediated by geometric confinement

Hua Zhang,Ruixia Hou,Peng Xiao,Rubo Xing,Tao Chen,Yanchun Han,Penggang Ren,Jun Fu

The migration dynamics of cells plays a key role in tissue engineering and regenerative medicine. Previous studies mostly focus on regulating stem cell fate and phenotype by biophysical cues. In contrast, less is known about how the geometric cues mediate the migration dynamics of cells. Here, we fabricate graphene oxide (GO) microstripes on cell non-adhesive PEG substrate by using micromolding in capillary (MIMIC) method. Such micropatterns with alternating cell adhesion and cell resistance enable an effective control of selective adhesion and migration of single cells. The sharp contrast in cell adhesion minimizes the invasion of cells into the PEG patterns, and thereby strongly confines the cells on GO microstripes. As a result, the cells are forced to adapt highly polarized, elongated, and oriented geometry to fit the patterns. A series of pattern widths have been fabricated to modulate the extent of cell deformation and polarization. Under strong confinement, the cytoskeleton contractility, intracellular traction, and actin filament elongation are highly promoted, which result in enhanced cell migration along the patterns. This work provides an important insight into developing combinatorial graphene-based patterns for the control of cell migration dynamics, which is of great significance for tissue engineering and regenerative medicine.

CAS / MDL: 7782-42-5 26570-48-9
研究领域: 生物医学工程 · 组织工程 · 再生医学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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CELL · 2024 · IF 45.5

Spatiotemporal modeling of molecular holograms

Xiaojie Qiu,Daniel Y. Zhu,Yifan Lu,Jiajun Yao,Zehua Jing,Kyung Hoi Min,Mengnan Cheng,Hailin Pan,Lulu Zuo,Samuel King,Qi Fang,Huiwen Zheng,Mingyue Wang,Shuai Wang,Qingquan Zhang,Sichao Yu,Sha Liao,Chao Liu,Xinchao Wu,Yiwei Lai,Shijie Hao,Zhewei Zhang,Liang Wu,Yong Zhang,Mei Li,Zhencheng Tu,Jinpei Lin,Zhuoxuan Yang,Yuxiang Li,Ying Gu,David Ellison,Ao Chen,Longqi Liu,Jonathan S. Weissman,Jiayi Ma,Xun Xu,Shiping Liu,Yinqi Bai

Quantifying spatiotemporal dynamics during embryogenesis is crucial for understanding congenital diseases. We developed Spateo ( https://github.com/aristoteleo/spateo-release ), a 3D spatiotemporal modeling framework, and applied it to a 3D mouse embryogenesis atlas at E9.5 and E11.5, capturing eight million cells. Spateo enables scalable, partial, non-rigid alignment, multi-slice refinement, and mesh correction to create molecular holograms of whole embryos. It introduces digitization methods to uncover multi-level biology from subcellular to whole organ, identifying expression gradients along orthogonal axes of emergent 3D structures, e.g., secondary organizers such as midbrain-hindbrain boundary (MHB). Spateo further jointly models intercellular and intracellular interaction to dissect signaling landscapes in 3D structures, including the zona limitans intrathalamica (ZLI). Lastly, Spateo introduces “morphometric vector fields” of cell migration and integrates spatial differential geometry to unveil molecular programs underlying asymmetrical murine heart organogenesis and others, bridging macroscopic changes with molecular dynamics. Thus, Spateo enables the study of organ ecology at a molecular level in 3D space over time.

CAS / MDL: 79-09-4
研究领域: 生物信息学 · 发育生物学 · 系统生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Nutrients · 2023 ·Vol. 15 ·期 2 ·378 · IF 5.9

Sea Cucumber Derived Triterpenoid Glycoside Frondoside A: A Potential Anti-Bladder Cancer Drug

Ruizhen Ru,Gengzhan Chen,Xiaoxia Liang,Xudong Cao,Lihong Yuan,Minjie Meng

Bladder cancer is a highly recurrent disease and a common cause of cancer-related deaths worldwide. Despite recent developments in diagnosis and therapy, the clinical outcome of bladder cancer remains poor; therefore, novel anti-bladder cancer drugs are urgently needed. Natural bioactive substances extracted from marine organisms such as sea cucumbers, scallops, and sea urchins are believed to have anti-cancer activity with high effectiveness and less toxicity. Frondoside A is a triterpenoid glycoside isolated from sea cucumber,Cucumaria frondosa. It has been demonstrated that Frondoside A exhibits anti-proliferative, anti-invasive, anti-angiogenic, anti-cancer, and potent immunomodulatory effects. In addition, CpG oligodeoxynucleotide (CpG-ODN) has also been shown to have potent anti-cancer effects in various tumors models, such as liver cancer, breast cancer, and bladder cancer. However, very few studies have investigated the effectiveness of Frondoside A against bladder cancer alone or in combination with CpG-ODN. In this study, we first investigated the individual effects of both Frondoside A and CpG-ODN and subsequently studied their combined effects on human bladder cancer cell viability, migration, apoptosis, and cell cycle in vitro, and on tumor growth in nude mice using human bladder cancer cell line UM-UC-3. To interrogate possible synergistic effects, combinations of different concentrations of the two drugs were used. Our data showed that Frondoside A decreased the viability of bladder cancer cells UM-UC-3 in a concentration-dependent manner, and its inhibitory effect on cell viability (2.5 μM) was superior to EPI (10 μM). We also showed that Frondoside A inhibited UM-UC-3 cell migration, affected the distribution of cell cycle and induced cell apoptosis in concentration-dependent manners, which effectively increased the sub-G1 (apoptotic) cell fraction. In addition, we also demonstrated that immunomodulator CpG-ODN could synergistically potentiate the inhibitory effects of Frondoside A on the proliferation and migration of human bladder cancer cell line UM-UC-3. In in vivo experiments, Frondoside A (800 μg/kg/day i.p. for 14 days) alone and in combination with CpG-ODN (1 mg/kg/dose i.p.) significantly decreased the growth of UM-UC-3 tumor xenografts, without any significant toxic side-effects; however, the chemotherapeutic agent EPI caused weight loss in nude mice. Taken together, these findings indicated that Frondoside A in combination with CpG-ODN is a promising therapeutic strategy for bladder cancer.Keywords:bladder cancer;Frondoside A;CpG oligodexynucleotides;cell viability;apoptosis;cell migration

CAS / MDL: 56390-09-1
研究领域: 肿瘤学 · 药理学 · 免疫学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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