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受整合素-细胞骨架-细胞核轴上机械转导作用影响而兴起的机械医学。

Emerging mechanomedicines informed by mechanotransduction along the integrin-cytoskeleton-nucleus axis.

作者信息

Yokoyama Yuka, Domkam Nya, Kabir Hannaneh, Mansour Abdullah, Tsukamoto Shingo, Yerima Ghafar, Adachi Taiji, Mofrad Mohammad R K

机构信息

Molecular Cell Biomechanics Laboratory, Departments of Bioengineering and Mechanical Engineering, University of California, Berkeley, California 94720, USA.

出版信息

APL Bioeng. 2025 Jun 10;9(2):021503. doi: 10.1063/5.0255473. eCollection 2025 Jun.


DOI:10.1063/5.0255473
PMID:40502441
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12158467/
Abstract

Mechanical forces are fundamental to the formation of normal biological tissues and the maintenance of physiological health. These forces are transmitted from the extracellular environment to the cell interior through cell-cell and cell-ECM interactions, the cytoskeleton, the LINC complex, the nuclear pore complex, and chromatin, ultimately regulating gene expression via transcription factors. This process, known as mechanotransduction, enables cells to convert mechanical signals into biochemical responses. Due to its critical role in various cellular functions and its influence on disease progression, mechanotransduction emerges as a potential therapeutic target for a range of conditions, including cancer and cardiovascular diseases, by integrating it with biochemistry, molecular biology, and genetics. Mechanomedicine, a burgeoning field, seeks to harness insights from mechanobiology to develop innovative diagnostic and therapeutic strategies. By targeting the molecular and cellular mechanisms underlying mechanotransduction, mechanomedicine aims to create more effective and precise treatments. Despite the potential, current clinical practices largely depend on conventional therapies like chemotherapy, underscoring the challenges of manipulating mechanotransducive pathways within living organisms. This review bridges fundamental mechanotransduction mechanisms with emerging therapeutic approaches, highlighting how mechanomedicine can revolutionize clinical practice. It explores the latest advancements in targeting mechanotransducive elements, discusses the therapeutic efficacy demonstrated in preclinical and clinical studies, and identifies future directions for integrating mechanobiological principles into medical treatments. By connecting basic mechanobiology with clinical applications, mechanomedicine holds the promise of offering targeted and reliable treatment options, ultimately transforming the landscape of disease management and patient care.

摘要

机械力对于正常生物组织的形成和生理健康的维持至关重要。这些力通过细胞间和细胞与细胞外基质的相互作用、细胞骨架、LINC复合体、核孔复合体和染色质从细胞外环境传递到细胞内部,最终通过转录因子调节基因表达。这个过程,即机械转导,使细胞能够将机械信号转化为生化反应。由于其在各种细胞功能中的关键作用以及对疾病进展的影响,通过将机械转导与生物化学、分子生物学和遗传学相结合,它成为一系列疾病(包括癌症和心血管疾病)的潜在治疗靶点。机械医学是一个新兴领域,旨在利用机械生物学的见解来开发创新的诊断和治疗策略。通过针对机械转导的分子和细胞机制,机械医学旨在创造更有效、更精确的治疗方法。尽管有潜力,但目前的临床实践在很大程度上依赖于化疗等传统疗法,这凸显了在活生物体中操纵机械转导途径的挑战。这篇综述将基本的机械转导机制与新兴的治疗方法联系起来,强调了机械医学如何能够彻底改变临床实践。它探讨了靶向机械转导元件的最新进展,讨论了临床前和临床研究中显示的治疗效果,并确定了将机械生物学原理整合到医学治疗中的未来方向。通过将基础机械生物学与临床应用联系起来,机械医学有望提供有针对性且可靠的治疗选择,最终改变疾病管理和患者护理的局面。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52cb/12158467/8b1dcf253375/ABPID9-000009-021503_1-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52cb/12158467/427a5818c992/ABPID9-000009-021503_1-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52cb/12158467/e0fb159e0df9/ABPID9-000009-021503_1-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52cb/12158467/8b1dcf253375/ABPID9-000009-021503_1-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52cb/12158467/427a5818c992/ABPID9-000009-021503_1-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52cb/12158467/e0fb159e0df9/ABPID9-000009-021503_1-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52cb/12158467/8b1dcf253375/ABPID9-000009-021503_1-g003.jpg

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Emerging mechanomedicines informed by mechanotransduction along the integrin-cytoskeleton-nucleus axis.

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本文引用的文献

[1]
Role of pore dilation in molecular transport through the nuclear pore complex: Insights from polymer scaling theory.

PLoS Comput Biol. 2025-4-7

[2]
Editorial: Mechanotransduction in vascular development and disease.

Front Physiol. 2024-12-10

[3]
The condensation of HP1α/Swi6 imparts nuclear stiffness.

Cell Rep. 2024-7-23

[4]
An in-silico study on the mechanical behavior of colorectal cancer cell lines in the micropipette aspiration process.

Comput Biol Med. 2024-8

[5]
Integrin mechanosensing relies on a pivot-clip mechanism to reinforce cell adhesion.

Biophys J. 2024-8-20

[6]
Bexotegrast in Patients with Idiopathic Pulmonary Fibrosis: The INTEGRIS-IPF Clinical Trial.

Am J Respir Crit Care Med. 2024-8-15

[7]
Tissue flows are tuned by actomyosin-dependent mechanics in developing embryos.

PRX Life. 2023

[8]
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J Cell Sci. 2024-5-1

[9]
Direct and selective pharmacological disruption of the YAP-TEAD interface by IAG933 inhibits Hippo-dependent and RAS-MAPK-altered cancers.

Nat Cancer. 2024-7

[10]
Chondrocyte hypertrophy in the growth plate promotes stress anisotropy affecting long bone development through chondrocyte column formation.

Bone. 2024-5

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