Xiaoxiao Chen, Youjun Xia, Wenqiang Du, Han Liu, Ran Hou, Yiyu Song, Wenhu Xu, Yuxin Mao, Jianfeng Chen
{"title":"接触引导在介观尺度上推动细胞向上迁移。","authors":"Xiaoxiao Chen, Youjun Xia, Wenqiang Du, Han Liu, Ran Hou, Yiyu Song, Wenhu Xu, Yuxin Mao, Jianfeng Chen","doi":"10.1007/s12195-023-00766-y","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>Cancer metastasis is associated with increased cancer incidence, recurrence, and mortality. The role of cell contact guidance behaviors in cancer metastasis has been recognized but has not been elucidated yet.</p><p><strong>Methods: </strong>The contact guidance behavior of cancer cells in response to topographical constraints is identified using microgrooved substrates with varying dimensions at the mesoscopic scale. Then, the cell morphology is determined to quantitatively analyze the effects of substrate dimensions on cells contact guidance. Cell density and migrate velocity signatures within the cellular population are determined using time-lapse phase-contrast microscopy. The effect of soluble factors concentration is determined by culturing cells upside down. Then, the effect of cell-substrate interaction on cell migration is investigated using traction force microscopy.</p><p><strong>Results: </strong>With increasing depth and decreasing groove width, cell elongation and alignment are enhanced, while cell spreading is inhibited. Moreover, cells display preferential distribution on the ridges, which is found to be more pronounced with increasing depth and groove width. Determinations of cell density and migration velocity signatures reveal that the preferential distribution on ridges is caused by cell upward migration. Combined with traction force measurement, we find that migration toward ridges is governed by different cell-substrate interactions between grooves and ridges caused by geometrical constraints. Interestingly, the upward migration of cells at the mesoscopic scale is driven by entropic maximization.</p><p><strong>Conclusions: </strong>The mesoscopic cell contact guidance mechanism based on the entropic force driven theory provides basic support for the study of cell alignment and migration along healthy tissues with varying size, thereby aiding in the prediction of cancer metastasis.</p><p><strong>Graphical abstract: </strong></p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s12195-023-00766-y.</p>","PeriodicalId":9687,"journal":{"name":"Cellular and molecular bioengineering","volume":"16 3","pages":"205-218"},"PeriodicalIF":2.3000,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10338420/pdf/","citationCount":"0","resultStr":"{\"title\":\"Contact Guidance Drives Upward Cellular Migration at the Mesoscopic Scale.\",\"authors\":\"Xiaoxiao Chen, Youjun Xia, Wenqiang Du, Han Liu, Ran Hou, Yiyu Song, Wenhu Xu, Yuxin Mao, Jianfeng Chen\",\"doi\":\"10.1007/s12195-023-00766-y\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>Cancer metastasis is associated with increased cancer incidence, recurrence, and mortality. The role of cell contact guidance behaviors in cancer metastasis has been recognized but has not been elucidated yet.</p><p><strong>Methods: </strong>The contact guidance behavior of cancer cells in response to topographical constraints is identified using microgrooved substrates with varying dimensions at the mesoscopic scale. Then, the cell morphology is determined to quantitatively analyze the effects of substrate dimensions on cells contact guidance. Cell density and migrate velocity signatures within the cellular population are determined using time-lapse phase-contrast microscopy. The effect of soluble factors concentration is determined by culturing cells upside down. Then, the effect of cell-substrate interaction on cell migration is investigated using traction force microscopy.</p><p><strong>Results: </strong>With increasing depth and decreasing groove width, cell elongation and alignment are enhanced, while cell spreading is inhibited. Moreover, cells display preferential distribution on the ridges, which is found to be more pronounced with increasing depth and groove width. Determinations of cell density and migration velocity signatures reveal that the preferential distribution on ridges is caused by cell upward migration. Combined with traction force measurement, we find that migration toward ridges is governed by different cell-substrate interactions between grooves and ridges caused by geometrical constraints. Interestingly, the upward migration of cells at the mesoscopic scale is driven by entropic maximization.</p><p><strong>Conclusions: </strong>The mesoscopic cell contact guidance mechanism based on the entropic force driven theory provides basic support for the study of cell alignment and migration along healthy tissues with varying size, thereby aiding in the prediction of cancer metastasis.</p><p><strong>Graphical abstract: </strong></p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s12195-023-00766-y.</p>\",\"PeriodicalId\":9687,\"journal\":{\"name\":\"Cellular and molecular bioengineering\",\"volume\":\"16 3\",\"pages\":\"205-218\"},\"PeriodicalIF\":2.3000,\"publicationDate\":\"2023-05-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10338420/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cellular and molecular bioengineering\",\"FirstCategoryId\":\"5\",\"ListUrlMain\":\"https://doi.org/10.1007/s12195-023-00766-y\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2023/6/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q3\",\"JCRName\":\"BIOPHYSICS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cellular and molecular bioengineering","FirstCategoryId":"5","ListUrlMain":"https://doi.org/10.1007/s12195-023-00766-y","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/6/1 0:00:00","PubModel":"eCollection","JCR":"Q3","JCRName":"BIOPHYSICS","Score":null,"Total":0}
Contact Guidance Drives Upward Cellular Migration at the Mesoscopic Scale.
Introduction: Cancer metastasis is associated with increased cancer incidence, recurrence, and mortality. The role of cell contact guidance behaviors in cancer metastasis has been recognized but has not been elucidated yet.
Methods: The contact guidance behavior of cancer cells in response to topographical constraints is identified using microgrooved substrates with varying dimensions at the mesoscopic scale. Then, the cell morphology is determined to quantitatively analyze the effects of substrate dimensions on cells contact guidance. Cell density and migrate velocity signatures within the cellular population are determined using time-lapse phase-contrast microscopy. The effect of soluble factors concentration is determined by culturing cells upside down. Then, the effect of cell-substrate interaction on cell migration is investigated using traction force microscopy.
Results: With increasing depth and decreasing groove width, cell elongation and alignment are enhanced, while cell spreading is inhibited. Moreover, cells display preferential distribution on the ridges, which is found to be more pronounced with increasing depth and groove width. Determinations of cell density and migration velocity signatures reveal that the preferential distribution on ridges is caused by cell upward migration. Combined with traction force measurement, we find that migration toward ridges is governed by different cell-substrate interactions between grooves and ridges caused by geometrical constraints. Interestingly, the upward migration of cells at the mesoscopic scale is driven by entropic maximization.
Conclusions: The mesoscopic cell contact guidance mechanism based on the entropic force driven theory provides basic support for the study of cell alignment and migration along healthy tissues with varying size, thereby aiding in the prediction of cancer metastasis.
Graphical abstract:
Supplementary information: The online version contains supplementary material available at 10.1007/s12195-023-00766-y.
期刊介绍：
The field of cellular and molecular bioengineering seeks to understand, so that we may ultimately control, the mechanical, chemical, and electrical processes of the cell. A key challenge in improving human health is to understand how cellular behavior arises from molecular-level interactions. CMBE, an official journal of the Biomedical Engineering Society, publishes original research and review papers in the following seven general areas:
Molecular: DNA-protein/RNA-protein interactions, protein folding and function, protein-protein and receptor-ligand interactions, lipids, polysaccharides, molecular motors, and the biophysics of macromolecules that function as therapeutics or engineered matrices, for example.
Cellular: Studies of how cells sense physicochemical events surrounding and within cells, and how cells transduce these events into biological responses. Specific cell processes of interest include cell growth, differentiation, migration, signal transduction, protein secretion and transport, gene expression and regulation, and cell-matrix interactions.
Mechanobiology: The mechanical properties of cells and biomolecules, cellular/molecular force generation and adhesion, the response of cells to their mechanical microenvironment, and mechanotransduction in response to various physical forces such as fluid shear stress.
Nanomedicine: The engineering of nanoparticles for advanced drug delivery and molecular imaging applications, with particular focus on the interaction of such particles with living cells. Also, the application of nanostructured materials to control the behavior of cells and biomolecules.
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