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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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Materials Today Bio · 2024 · IF 8.7

Spatial confinement modulates endothelial cell behavior and traction force in 3D hydrogel microgrooves

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.

CAS / MDL: 188968-51-6
研究领域: 生物力学 · 细胞生物学 · 血管生物学
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Biology-Basel · 2024 ·Vol. 13 ·期 5 ·357 · IF 3.6

α-Catenin and Piezo1 Mediate Cell Mechanical Communication via Cell Adhesions

Mingxing Ouyang,Qingyu Zhang,Yiming Zhu,Mingzhi Luo,Bing Bu,Linhong Deng

Simple Summaryα-Catenin mediates cell-matrix interactions while Piezo1 at focal adhesions likely mechanosenses traction force through the matrix hydrogel during cell mechanical communication.AbstractCell-to-cell distant mechanical communication has been demonstrated using in vitro and in vivo models. However, the molecular mechanisms underlying long-range cell mechanoresponsive interactions remain to be fully elucidated. This study further examined the roles of α-Catenin and Piezo1 in traction force-induced rapid branch assembly of airway smooth muscle (ASM) cells on a Matrigel hydrogel containing type I collagen. Our findings demonstrated that siRNA-mediated downregulation of α-Catenin or Piezo1 expression or chemical inhibition of Piezo1 activity significantly reduced both directional cell movement and branch assembly. Regarding the role of N-cadherin in regulating branch assembly but not directional migration, our results further confirmed that siRNA-mediated downregulation of α-Catenin expression caused a marked reduction in focal adhesion formation, as assessed by focal Paxillin and Integrin α5 localization. These observations imply that mechanosensitive α-Catenin is involved in both cell–cell and cell-matrix adhesions. Additionally, Piezo1 partially localized in focal adhesions, which was inhibited by siRNA-mediated downregulation of α-Catenin expression. This result provides insights into the Piezo1-mediated mechanosensing of traction force on a hydrogel. Collectively, our findings highlight the significance of α-Catenin in the regulation of cell-matrix interactions and provide a possible interpretation of Piezo1-mediated mechanosensing activity at focal adhesions during cell–cell mechanical communication.

CAS / MDL: 10138-52-0
研究领域: 细胞生物学 · 生物力学
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Nature Communications · 2024 ·Vol. 15 ·期 1 ·1-10 · IF 14.7

Chaperone solvent-assisted assembly of polymers at the interface of two immiscible liquids

Zhao Sai,Jiang Yongkang,Fu Yuchen,Chen Wei,Zhang Qinrong,He Liulin,Huang Changxiong,Liu Yao,Zeng Xiao Cheng,Chai Yu

The assembly of polymers at liquid-liquid interfaces offers a promising strategy for fabricating two-dimensional polymer films. However, a significant challenge arises when the polymers lack inherent interfacial traction. In response, we introduce an approach termed chaperone solvent-assisted assembly. This approach utilizes a target polymer, X, along with three solvents: α, β, and γ. α and β are poor solvents for X and immiscible with each other, while γ is a good solvent for X and miscible with both α and β, thus serving as the chaperone solvent. The cross-interface diffusion of γ induces the assembly of interfacially nonactive X at the α-β interface, and this mechanism is verified through systematic in situ and ex situ studies. We show that chaperone solvent-assisted assembly is versatile and reliable for the interfacial assembly of polymers, including those that are interfacially nonactive. Several practical applications based on chaperone solvent-assisted assembly are also demonstrated.

研究领域: 材料科学 · 聚合物化学 · 界面科学
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Advanced Healthcare Materials · 2023 · IF 10

Direct Mapping of Cytomechanical Homeostasis Destruction in Osteoarthritis Based on Silicon Nanopillar Array

Dengjie Yu,Qingbin Nie,Jiangtao Xue,Ruizeng Luo,Shiwang Xie,Shengyu Chao,Engui Wang,Linlin Xu,Yizhu Shan,Zhuo Liu,Yusheng Li,Zhou Li

Osteoarthritis (OA) is the most prevalent joint degenerative disease characterized by chronic joint inflammation. The pathogenesis of OA has not been fully elucidated yet. Cartilage erosion is the most significant pathological feature in OA, which is considered as the result of the cytomechanical homeostasis destruction. The cytomechanical homeostasis is maintained by the dynamic interaction between cells and the extracellular matrix, which can be reflected by cell traction force (CTF). It is critical to assess the CTF for providing a deeper understanding of the cytomechanical homeostasis destruction and progression in OA. In this study, a silicon nanopillar array (Si-NP) with high spatial resolution and aspect ratio is fabricated to investigate the CTF in response to OA. We discover the CTF is degraded in OA, which is attributed to the F-actin reorganization induced by the activation of RhoA/ROCK signaling pathway. Si-NP also show promising potential as a mechanopharmacological assessment platform for OA drug screening and evaluation. This article is protected by copyright. All rights reserved

CAS / MDL: 13739-02-1
研究领域: 骨科 · 生物力学 · 纳米技术 · 药理学
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BIOMACROMOLECULES · 2021 · IF 6.988

Adsorption Force of Fibronectin: A Balance Regulator to Transmission of Cell Traction Force and Fluid Shear Stress

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
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Journal of Materials Chemistry B · 2024 · IF 6.1

Revelation of Adhesive Proteins Affecting Cellular Contractility through A Reference-free Traction Force Microscopy

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 · 生物物理学 · 生物材料科学 · 机械生物学
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BIOMATERIALS · 2018 · IF 8.806

Adsorption force of fibronectin controls transmission of cell traction force and subsequent stem cell fate

Manping Lin,Shilong Mao,Jinfeng Wang,Juan Xing,Yuanliang Wang,Kaiyong Cai,Yanfeng Luo

The transmission of cell traction force (CTF) to underlying biomaterials is essential for adhered cells to measure and respond to their mechanical microenvironment . Given that the protein layer adsorbed on materials lies between the cells and materials, we hypothesize that the interfacial strength of protein-material interfaces (i.e., the adsorption force of proteins, F ad ) should have an important role in regulating the transmission of CTF. To test this hypothesis, rat mesenchymal stem cells (rMSCs) were cultured on poly(dimethyl siloxane) (PDMS) substrates with different F ad of fibronectin (FN), and the transmission of CTF was observed by immunofluorescence staining of FN and deformation of PDMS. As revealed, FN on substrates with low F ad is more liable to be desorbed by CTF, which prevents the transmission of CTF to substrates. In contrast, high F ad facilitates the transmission of CTF from rMSCs to the FN layer and PDMS substrates so that rMSCs can perceive the mechanical properties of substrates. We further demonstrated that the divergent transmission of CTF on low and high F ad substrates regulates the lineage specifications of rMSCs. Our study confirms the important role of F ad in CTF transmission and provides a new perspective to gain insights into cell-material interactions and cell fates, which may help to guide the design of better biomaterials.

研究领域: 生物材料科学 · 细胞生物学 · 组织工程
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