Mechanobiology in Medicine最新文献_第2页

A practical protocol of processing mineralized tissue for Visium spatial transcriptomics 一个实用的协议处理矿化组织的视觉空间转录组学

Mechanobiology in Medicine

Pub Date : 2025-11-04 DOI: 10.1016/j.mbm.2025.100163

Jixing Miao , Mingjie Ma , Yuhan Guo , Ling Qin , Lutian Yao

Spatial transcriptomics analysis of mineralized tissues faces significant challenges due to lengthy decalcification procedures that severely compromise RNA integrity and subsequent gene detection. This protocol details an optimized workflow to process bone and fracture callus samples for 10x Genomics Visium spatial transcriptomics. The key innovation involves replacing conventional EDTA decalcification with Morse's solution, enabling rapid decalcification (<24 h) while preserving RNA quality, as evidenced by a favorable DV200 value. Additionally, the protocol emphasizes the critical use of SCHOTT NEXTERION® Slide H (3-D hydrogel-coated) to maximize adherence of fragile decalcified bone sections during processing, preventing detachment and preserving morphological integrity. We applied this optimized method to intact and fractured mouse femurs. The results demonstrate a substantial improvement in transcript capture efficiency: Visium V2 yielded an average of 5639 genes per spot, while Visium HD achieved an average of 170 genes per 8 μm bin (equivalent to ∼4100 genes per 55 μm spot). This step-by-step protocol overcomes major pre-analytical hurdles, enabling high-resolution spatial transcriptomic profiling of mineralized tissues with significantly enhanced data quality.

矿化组织的空间转录组学分析面临着巨大的挑战，因为漫长的脱钙过程严重损害了RNA的完整性和随后的基因检测。本协议详细介绍了一个优化的工作流程，以处理骨和骨折骨痂样本的10x Genomics Visium空间转录组学。关键的创新在于用莫尔斯溶液取代传统的EDTA脱钙，实现快速脱钙（24小时），同时保持RNA质量，DV200值有利。此外，该方案强调了SCHOTT NEXTERION®Slide H （3d水凝胶涂层）的关键使用，以在加工过程中最大限度地粘附脆弱的脱钙骨切片，防止脱离并保持形态完整性。我们将这种优化的方法应用于完整和骨折的小鼠股骨。结果表明转录本捕获效率有了实质性的提高：Visium V2平均每个位点产生5639个基因，而Visium HD平均每8 μm bin产生170个基因（相当于每55 μm位点产生4100个基因）。这个循序渐进的方案克服了主要的分析前障碍，实现了矿化组织的高分辨率空间转录组分析，显著提高了数据质量。

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引用次数: 0

Magnesium-containing implants enhance bone healing: A mechanobiological perspective 含镁植入物促进骨愈合：机械生物学的观点

Mechanobiology in Medicine

Pub Date : 2025-10-20 DOI: 10.1016/j.mbm.2025.100161

Zhenkang Wen , Lei Lei , Haozhi Zhang , Zheyu Jin , Zhengming Shan , Weiyang Liu , Wenxue Tong , Jiankun Xu , Ling Qin

Unlike traditional implants primarily composed of bioinert materials, magnesium (Mg) -a degradable biomaterial - offers significant promise for next-generation bone healing implants, whether utilized as a primary structural component or a supporting material. While most research focuses on Mg's bioactive and osteoimmunological effect, this review highlights its mechanobiological role, summarizing the merits of Mg-containing implants in facilitating mechanotransduction and associated cellular events during the bone healing. Beyond introducing Mg's biomechanical benefits in preventing stress shielding, this review synthesizes its unique attributes: exceptional bone-implant integration and synergistic effects with physical stimuli to amplify new bone formation. Crucially, we also summarize the activation of mechanotransduction signaling pathways, providing a mechanistic basis for Mg's positive mechanobiological influence. Finally, we discuss challenges arising from the interaction between physical loading and Mg degradation, alongside future perspectives and potential solutions to bridge the gap between theory and clinical application, thereby accelerating translation applications of Mg-containing implants.

与主要由生物惰性材料组成的传统植入物不同，镁（Mg）是一种可降解的生物材料，无论是作为主要结构成分还是支撑材料，都为下一代骨愈合植入物提供了重要的前景。虽然大多数研究都集中在镁的生物活性和骨免疫作用上，但本文综述了其机械生物学作用，总结了含镁植入物在促进骨愈合过程中的机械转导和相关细胞事件方面的优点。除了介绍镁在防止应力屏蔽方面的生物力学益处外，本文还综合了其独特的属性：特殊的骨-种植体整合和与物理刺激的协同效应，以扩大新骨的形成。重要的是，我们还总结了机械转导信号通路的激活，为Mg的积极机械生物学影响提供了机制基础。最后，我们讨论了物理负载和Mg降解之间相互作用所带来的挑战，以及未来的观点和潜在的解决方案，以弥合理论和临床应用之间的差距，从而加速含Mg植入物的翻译应用。

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引用次数: 0

Synthetic mechanoreceptor engineering: From genetic encoding to DNA nanotechnology-based reprogramming 合成机械受体工程：从遗传编码到基于DNA纳米技术的重编程

Mechanobiology in Medicine

Pub Date : 2025-10-06 DOI: 10.1016/j.mbm.2025.100160

Sihui Yang , Zhou Nie

Precise modulation of mechanoreceptor-mediated signal transduction is crucial for decoding cellular mechanotransduction mechanisms and programming cell fate. This review provides a comprehensive summary of recent advances in engineering synthetic mechanoreceptors, spanning from protein-centric genetic encoding to DNA nanotechnology-based non-genetic reprogramming strategies. Genetic engineering strategies employ protein structure encoding and site-directed mutagenesis to reprogram force-response functions in natural mechanoreceptors. As a complementary non-genetic approach, DNA nanotechnology leverages its programmability, modularity, and predictable mechanical properties to achieve precise control over receptor functionalities. The flourishing development of DNA mechanosensitive nanodevices has provided a promising synthetic toolkit for manipulating mechanoreceptors, enabling precise control over receptor spatial organization and signal transduction. A key innovation is the development of novel DNA-functionalized artificial mechanoreceptors (AMRs), which confer force-responsiveness to naturally non-mechanosensitive receptors without genetic modification, thereby enabling customized mechanotransduction and mechanobiological applications. Collectively, this paradigm shift highlights DNA-based non-genetic receptor engineering as a versatile and powerful toolkit, paving new avenues for mechanobiology research and pioneering force-directed therapeutic strategies in regenerative medicine.

机械受体介导的信号转导的精确调节对于解码细胞机械转导机制和编程细胞命运至关重要。本文综述了工程合成机械感受器的最新进展，从以蛋白质为中心的遗传编码到基于DNA纳米技术的非遗传重编程策略。基因工程策略采用蛋白质结构编码和定点诱变来重编程自然机械感受器的力响应功能。作为一种互补的非遗传方法，DNA纳米技术利用其可编程性、模块化和可预测的机械特性来实现对受体功能的精确控制。DNA机械敏感纳米器件的蓬勃发展为操纵机械感受器提供了一个有前途的合成工具包，使精确控制受体的空间组织和信号转导成为可能。一项关键的创新是新型dna功能化人工机械感受器（AMRs）的发展，它在没有基因修饰的情况下赋予自然非机械敏感感受器力响应性，从而实现定制的机械转导和机械生物学应用。总的来说，这种范式转变突出了基于dna的非遗传受体工程作为一个多功能和强大的工具箱，为机械生物学研究和再生医学中先锋力导向治疗策略铺平了新的道路。

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引用次数: 0

Multimodal mechanoregulation strategies towards tissue regeneration 组织再生的多模式机械调控策略

Mechanobiology in Medicine

Pub Date : 2025-09-25 DOI: 10.1016/j.mbm.2025.100159

Qifan Yu , Yudong Duan , Zhuang Zhu , Wei Ji , Caihong Zhu , Bin Li

Mechanical microenvironment of each tissue plays an important role in regulating its special cellular behaviors, such as morphology, proliferation, differentiation, and migration. Mechanical signals can direct lineage specification or promote cell migration towards injury sites and facilitate tissue repair. During tissue regeneration, mechanoregulation is also important due to the ability of providing an extracellular microenvironment that closely resembles the physiological state for cells. Currently, mechanoregulation strategies have been usually applied to promote tissue regeneration. However, the in vivo mechanical environment is highly complex, these single mechanical conditioning strategies cannot comprehensively replicate the mechanical microenvironment experienced by cells or tissues in the body, thereby hindering the achievement of efficient tissue regeneration. The proposal of multimodal mechanoregulation strategies offers promising avenues to address this limitation. Herein, we summarize the critical role of mechanical factors in promoting tissue regeneration and the current development of different multimodal mechanoregulation approaches. Furthermore, the complex mechanical microenvironment of various tissues such as bone, intervertebral disc and cardiac. Afterwards, the recent successful applications of multimodal mechanical strategies in regenerative therapies were reviewed. And we delineate the persisting challenges, potential resolutions, and emerging translational prospects for multimodal mechanoregulation strategies in regenerative medicine, providing a reference for further development of multimodal mechanoregulation approaches.

每种组织的机械微环境对其形态、增殖、分化和迁移等特殊细胞行为起着重要的调节作用。机械信号可以指导谱系规范或促进细胞向损伤部位迁移，促进组织修复。在组织再生过程中，机械调节也很重要，因为它能够提供一个与细胞生理状态非常相似的细胞外微环境。目前，机械调节策略通常被用于促进组织再生。然而，体内机械环境是高度复杂的，这些单一的机械调节策略不能全面复制细胞或组织在体内所经历的机械微环境，从而阻碍了组织高效再生的实现。多模式机械调节策略的提议为解决这一限制提供了有希望的途径。在此，我们总结了机械因素在促进组织再生中的关键作用以及目前不同的多模态机械调节方法的发展。此外，骨、椎间盘、心脏等多种组织的复杂力学微环境。然后，回顾了近年来多模态机械策略在再生治疗中的成功应用。我们描述了再生医学中多模态机制调控策略的持续挑战、潜在解决方案和新兴的转化前景，为多模态机制调控方法的进一步发展提供参考。

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引用次数: 0

Substrate stiffness modulates phenotype-dependent fibroblast contractility and migration independent of TGF-β stimulation 底物硬度调节表型依赖性成纤维细胞的收缩性和迁移，独立于TGF-β刺激

Mechanobiology in Medicine

Pub Date : 2025-09-24 DOI: 10.1016/j.mbm.2025.100158

Mirko D'Urso , Pim van den Bersselaar , Sarah Pragnere , Paolo Maiuri , Carlijn V.C. Bouten , Nicholas A. Kurniawan

During wound healing, fibroblasts undergo radical processes that impact their phenotype and behavior. They are activated, recruited to the injury site, assume a contractile phenotype, and secrete extracellular matrix proteins to orchestrate tissue repair. Thus, fibroblast responses require dynamic changes in cytoskeleton assembly and organization, adhesion morphology, and force generation. At the same time, fibroblasts experience changes in environmental stiffness during tissue wounding and healing. Although cells are generally known to use their adhesion–contraction machinery to sense microenvironmental stiffness, little is known about how stiffness affects the fibroblast phenotypical transition and behavior in wound healing. Here we demonstrate that stiffness plays a deterministic role in determining fibroblast phenotype, surprisingly even overruling the classical TGF-β-mediated stimulation. By combining morphometric analysis, traction force microscopy, and single-cell migration analysis, we show that environmental stiffness primes the cytoskeletal and mechanical responses of fibroblasts, strongly modulating their morphology, force generation, and migration behavior. Our study, therefore, points to the importance of tissue stiffness as a key mechanobiological regulator of fibroblast behavior, thus serving as a potential target for controlling tissue repair.

在伤口愈合过程中，成纤维细胞经历影响其表型和行为的激进过程。它们被激活，被招募到损伤部位，呈现收缩表型，并分泌细胞外基质蛋白来协调组织修复。因此，成纤维细胞反应需要细胞骨架组装和组织、粘附形态和力产生的动态变化。同时，成纤维细胞在组织损伤和愈合过程中经历环境刚度的变化。虽然细胞通常使用它们的粘附-收缩机制来感知微环境的刚度，但对于刚度如何影响成纤维细胞在伤口愈合中的表型转变和行为，我们知之甚少。在这里，我们证明了硬度在决定成纤维细胞表型中起决定性作用，令人惊讶的是，甚至超过了经典的TGF-β介导的刺激。通过结合形态计量学分析、引力显微镜和单细胞迁移分析，我们发现环境刚度启动了成纤维细胞的细胞骨架和机械反应，强烈地调节了它们的形态、力的产生和迁移行为。因此，我们的研究指出了组织刚度作为成纤维细胞行为的关键机械生物学调节因子的重要性，因此可以作为控制组织修复的潜在靶点。

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引用次数: 0

Mechanotransduction in neutrophil: Mechanosensing and immune function regulation 中性粒细胞的机械转导：机械感应和免疫功能调节

Mechanobiology in Medicine

Pub Date : 2025-09-07 DOI: 10.1016/j.mbm.2025.100157

Wenying Zhao, Jin Wang, Jing Wang

Immune cells sense and transduce mechanical signals such as stiffness, stretch, compression, and shear stress. In the past few years, our understanding of the mechanosensitive signaling pathways in myeloid cells has significantly expanded, especially in monocytes, macrophages, and dendritic cells. Recently, the mechanobiological regulation of neutrophil function has been deciphered. Mechanical signals from tissue-derived shear stress and cellular deformation tension reprogram neutrophil transcription via GEF-H1, PIEZO1, and TRPV4 pathways, modulating neutrophil functions in homeostasis and trans-endothelial migration. Understanding these force-dependent processes provides novel insights into neutrophil plasticity and highlights potential therapeutic strategies and approaches for inflammatory and infectious diseases.

免疫细胞感知和转导机械信号，如刚度、拉伸、压缩和剪切应力。在过去的几年中，我们对髓细胞，特别是单核细胞、巨噬细胞和树突状细胞中机械敏感信号通路的理解有了显著的扩展。近年来，中性粒细胞功能的机械生物学调控已被破译。来自组织源性剪切应力和细胞变形张力的机械信号通过GEF-H1、PIEZO1和TRPV4途径重编程中性粒细胞转录，调节中性粒细胞在体内平衡和跨内皮迁移中的功能。了解这些力依赖过程提供了对中性粒细胞可塑性的新见解，并强调了炎症和感染性疾病的潜在治疗策略和方法。

引用次数: 0

Allosteric pockets in the measles and Nipah virus polymerases: Mechanobiological insights and AI-driven drug discovery opportunities 麻疹和尼帕病毒聚合酶的变构口袋：机械生物学见解和人工智能驱动的药物发现机会

Mechanobiology in Medicine

Pub Date : 2025-08-26 DOI: 10.1016/j.mbm.2025.100156

Yiru Wang , Lixia Zhao , Heqiao Zhang

Nonsegmented negative-sense RNA viruses (nsNSVs)—including highly pathogenic pathogens such as measles virus (MeV), Nipah virus (NiV), Hendra virus (HeV), Ebola virus (EBOV), and others—pose major global health threats, yet most lack approved antiviral therapeutics. In the recent study, high-resolution cryo-electron microscopy (cryo-EM) revealed previously unrecognized allosteric pockets in the large (L) polymerase proteins of MeV and NiV, spatially distinct from the catalytic nucleotide-binding site. We further demonstrated that the non-nucleoside inhibitor ERDRP-0519 engages these pockets to allosterically ‘lock’ the polymerase in a mechanically inactive state. These findings reveal an allosteric mechanism of inhibition rooted in the conformational mechanics of the enzyme and highlight opportunities for integrating artificial intelligence (AI)-aided drug discovery (AIDD) into rational drug design.

非分段负义RNA病毒（nsNSVs）——包括麻疹病毒（MeV）、尼帕病毒（NiV）、亨德拉病毒（HeV）、埃博拉病毒（EBOV）等高致病性病原体——对全球健康构成重大威胁，但大多数病毒缺乏经批准的抗病毒治疗方法。在最近的研究中，高分辨率冷冻电镜（cryo-EM）发现MeV和NiV的大(L)聚合酶蛋白中先前未被识别的变弹性口袋，在空间上与催化核苷酸结合位点不同。我们进一步证明，非核苷类抑制剂ERDRP-0519与这些小口袋结合，以变弹性“锁定”聚合酶，使其处于机械失活状态。这些发现揭示了基于酶的构象机制的抑制变构机制，并突出了将人工智能（AI）辅助药物发现（AIDD）整合到合理药物设计中的机会。

引用次数: 0

Theta-shaking mitigates cognitive-emotional decline via subiculum and ventral septum metabolic plasticity 脑波震动通过枕下和腹隔代谢可塑性减轻认知情绪下降

Mechanobiology in Medicine

Pub Date : 2025-08-22 DOI: 10.1016/j.mbm.2025.100148

Runhong Yao , Kouji Yamada , Hirohide Sawada , Takeshi Chihara , Naoki Aizu , Kazuhiro Nishii

Aging-associated cognitive decline remains a major challenge in gerontology; few non-invasive interventions provide both mechanistic insight and translational feasibility. We investigated whether low-frequency “theta-shaking” whole-body vibration (5 Hz) could modulate cognitive function, emotional behavior, and metabolic plasticity in a senescence-accelerated mouse model. Senescence-accelerated mouse prone-10 mice were exposed to theta-shaking stimulation for 30 weeks. Spatial memory was assessed using Y-maze spontaneous alternation test, and anxiety-related behavior was evaluated using marble burying test. Histological and immunohistochemical analyses were conducted to assess neuronal density and protein expression in specific brain regions. Theta-shaking subjected mice exhibited delayed yet significant improvements in spatial memory at 20 (p = 0.017) and 30 (p = 0.018) weeks. Anxiety-related behavior shows a biphasic pattern: an initial increase at 20 weeks (p < 0.001) followed by stabilization at 30 weeks. Histological analysis revealed preserved neuronal density in the subiculum (p < 0.001) and elevated proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) expression in the Cornu Ammonis 1, subiculum, and lateral septum (all p < 0.05). Notably, mitochondrial biogenesis appeared to be intervention's primary target, as shown by robust PGC1α upregulation, while brain-derived neurotrophic factor revealed a trend-level increase (p = 0.062), and neurotrophin-3 expression remained unchanged. Frequency-tuned mechanical stimulation induced region-specific neural neurometabolic adaptations, supporting theta-shaking as a non-pharmacological, low-exertion strategy to counteract brain aging. These findings offer promising translational potential, especially for individuals with limited mobility.

与衰老相关的认知能力下降仍然是老年学的主要挑战；很少有非侵入性干预既能提供机理见解又能提供转化可行性。在衰老加速小鼠模型中，我们研究了低频“抖theta”全身振动（5hz）是否可以调节认知功能、情绪行为和代谢可塑性。衰老加速小鼠倾向-10小鼠暴露于摇脑波刺激30周。采用y迷宫自发交替测验评估空间记忆，采用弹珠掩埋测验评估焦虑相关行为。通过组织学和免疫组织化学分析来评估特定脑区域的神经元密度和蛋白质表达。在第20周（p = 0.017）和第30周（p = 0.018）时，震荡实验小鼠在空间记忆方面表现出延迟但显著的改善。焦虑相关行为表现出双相模式：在20周时开始增加（p < 0.001），随后在30周时稳定下来。组织学分析显示，枕骨下的神经元密度保持不变（p < 0.001），鹦鹉角1、枕骨下和外侧隔的增殖因子激活受体γ辅助激活因子1- α (PGC1α)表达升高（p < 0.05）。值得注意的是，线粒体生物发生似乎是干预的主要目标，如PGC1α的强劲上调，而脑源性神经营养因子呈趋势水平升高（p = 0.062），神经营养因子-3的表达保持不变。频率调谐的机械刺激诱导了特定区域的神经代谢适应，支持theta-shaking作为一种非药物、低消耗的策略来对抗大脑衰老。这些发现提供了有希望的转化潜力，特别是对行动不便的个体。

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引用次数: 0

Fighting cardiac fibrosis using the chemomechanical method 利用化学力学方法对抗心脏纤维化

Mechanobiology in Medicine

Pub Date : 2025-08-16 DOI: 10.1016/j.mbm.2025.100147

Yunlong Huo

Diffuse myocardial fibrosis affects disease severity and outcomes in multiple heart diseases. A recent study in NATURE has shown a chemomechanical method to regulate myocardial stromal cell states to suppress fibrosis in vitro and in vivo, which provides a proof-of-concept therapeutic strategy. This study reviews the proposed chemomechanical method and other recent biotechnologies to fight cardiac fibrosis.

弥漫性心肌纤维化影响多种心脏疾病的严重程度和预后。《自然》杂志最近的一项研究表明，在体外和体内，一种化学力学方法可以调节心肌基质细胞状态以抑制纤维化，这提供了一种概念验证的治疗策略。本研究综述了提出的化学力学方法和其他最近的生物技术来对抗心脏纤维化。

引用次数: 0

Mitochondria power the nucleus under pressure 线粒体在压力下为细胞核提供能量

Mechanobiology in Medicine

Pub Date : 2025-08-12 DOI: 10.1016/j.mbm.2025.100146

Meng Yao , Yao Zong , Junjie Gao

Mechanical confinement of cells, as occurs during processes like tumor cell invasion or immune cell trafficking, poses a pressure that can threaten nuclear integrity and cell viability. Recent findings illuminate a rapid adaptive mechanism by which cells under acute compressive stress rearrange their internal architecture to preserve nuclear functions. Upon confinement, mitochondria swiftly relocate to cluster around the nucleus (forming nuclear-associated mitochondria, NAM), entrapped by a web of endoplasmic reticulum (ER) and actin filaments. This proximity provides a localized surge of ATP within the nucleus, fueling energy-intensive nuclear processes, notably maintaining an open chromatin state and facilitating efficient DNA damage repair. This targeted energy delivery maintains nuclear chromatin accessibility, supports DNA repair mechanisms, and ensures sustained cell proliferation despite physical constraints. Here we provide a commentary on these findings, discussing the biological significance of mitochondria–nucleus repositioning, the role of nuclear ATP in safeguarding chromatin, and the broader implications for cellular fitness in development and disease.

在肿瘤细胞侵袭或免疫细胞运输等过程中，对细胞的机械限制会造成威胁核完整性和细胞活力的压力。最近的研究结果阐明了一种快速适应机制，通过这种机制，细胞在急性压缩应力下重新排列其内部结构以保持核功能。禁闭后，线粒体迅速迁移到核周围聚集（形成核相关线粒体，NAM），被内质网（ER）和肌动蛋白丝所包围。这种接近提供了细胞核内ATP的局部激增，为能量密集型核过程提供燃料，特别是维持开放的染色质状态和促进有效的DNA损伤修复。这种有针对性的能量传递维持核染色质的可及性，支持DNA修复机制，并确保在物理限制下持续的细胞增殖。在这里，我们对这些发现进行评论，讨论线粒体-细胞核重新定位的生物学意义，核ATP在保护染色质中的作用，以及在发育和疾病中对细胞适应性的更广泛影响。

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引用次数: 0