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利用磁微机器人定量测量肿瘤集落和胚胎的硬度和力。

Quantifying stiffness and forces of tumor colonies and embryos using a magnetic microrobot.

机构信息

Department of Mechanical Science and Engineering, Grainger College of Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.

Key Laboratory of Molecular Biophysics of the Ministry of Education, Laboratory for Cellular Biomechanics and Regenerative Medicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei 430074, China.

出版信息

Sci Robot. 2023 Jan 25;8(74):eadc9800. doi: 10.1126/scirobotics.adc9800.


DOI:10.1126/scirobotics.adc9800
PMID:36696474
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10098875/
Abstract

Stiffness and forces are two fundamental quantities essential to living cells and tissues. However, it has been a challenge to quantify both 3D traction forces and stiffness (or modulus) using the same probe in vivo. Here, we describe an approach that overcomes this challenge by creating a magnetic microrobot probe with controllable functionality. Biocompatible ferromagnetic cobalt-platinum microcrosses were fabricated, and each microcross (about 30 micrometers) was trapped inside an arginine-glycine-apartic acid-conjugated stiff poly(ethylene glycol) (PEG) round microgel (about 50 micrometers) using a microfluidic device. The stiff magnetic microrobot was seeded inside a cell colony and acted as a stiffness probe by rigidly rotating in response to an oscillatory magnetic field. Then, brief episodes of ultraviolet light exposure were applied to dynamically photodegrade and soften the fluorescent nanoparticle-embedded PEG microgel, whose deformation and 3D traction forces were quantified. Using the microrobot probe, we show that malignant tumor-repopulating cell colonies altered their modulus but not traction forces in response to different 3D substrate elasticities. Stiffness and 3D traction forces were measured, and both normal and shear traction force oscillations were observed in zebrafish embryos from blastula to gastrula. Mouse embryos generated larger tensile and compressive traction force oscillations than shear traction force oscillations during blastocyst. The microrobot probe with controllable functionality via magnetic fields could potentially be useful for studying the mechanoregulation of cells, tissues, and embryos.

摘要

刚性和力是生命细胞和组织所必需的两个基本量。然而,使用相同的探针在体内定量测量 3D 牵引力和刚性(或模量)一直是一个挑战。在这里,我们描述了一种通过创建具有可控功能的磁性微机器人探针来克服这一挑战的方法。生物相容性的铁磁钴铂微十字被制造出来,并且每个微十字(约 30 微米)都被微流控设备捕获在一个精氨酸-甘氨酸-天冬氨酸偶联的刚性聚乙二醇(PEG)圆形微凝胶(约 50 微米)内部。刚性磁性微机器人被播种在细胞菌落内部,并通过在振荡磁场中刚性旋转充当刚性探针。然后,短暂的紫外线照射应用于动态光降解和软化荧光纳米颗粒嵌入的 PEG 微凝胶,其变形和 3D 牵引力被量化。使用微机器人探针,我们表明恶性肿瘤再填充细胞菌落改变了它们的模量,但对不同的 3D 基质弹性没有改变牵引力。测量了刚性和 3D 牵引力,并在从囊胚到原肠胚的斑马鱼胚胎中观察到了正常和剪切牵引力的振荡。与剪切牵引力振荡相比,在胚泡期,小鼠胚胎产生了更大的拉伸和压缩牵引力振荡。通过磁场具有可控功能的微机器人探针可能对研究细胞、组织和胚胎的机械调节具有重要意义。

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[7]
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[9]
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[10]
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本文引用的文献

[1]
Embryo model completes gastrulation to neurulation and organogenesis.

Nature. 2022-10

[2]
Nanoscale Tracking Combined with Cell-Scale Microrheology Reveals Stepwise Increases in Force Generated by Cancer Cell Protrusions.

Nano Lett. 2022-9-28

[3]
Spatial correlation of cell stiffness and traction forces in cancer cells measured with combined SICM and TFM.

RSC Adv. 2021-4-14

[4]
Telerobotic neurovascular interventions with magnetic manipulation.

Sci Robot. 2022-4-13

[5]
Depletion of aneuploid cells in human embryos and gastruloids.

Nat Cell Biol. 2021-4

[6]
Cytoskeletal prestress: The cellular hallmark in mechanobiology and mechanomedicine.

Cytoskeleton (Hoboken). 2021-6

[7]
Ex utero mouse embryogenesis from pre-gastrulation to late organogenesis.

Nature. 2021-5

[8]
Stress fiber anisotropy contributes to force-mode dependent chromatin stretching and gene upregulation in living cells.

Nat Commun. 2020-9-29

[9]
Mechanics of a multilayer epithelium instruct tumour architecture and function.

Nature. 2020-9-2

[10]
Zona pellucida shear modulus, a possible novel non-invasive method to assist in embryo selection during in-vitro fertilization treatment.

Sci Rep. 2020-8-21

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