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Trends in confinement-induced cell migration and multi-omics analysis

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Abstract

Cell migration is an essential manner of different cell lines that are involved in embryological development, immune responses, tumorigenesis, and metastasis in vivo. Physical confinement derived from crowded tissue microenvironments has pivotal effects on migratory behaviors. Distinct migration modes under a heterogeneous extracellular matrix (ECM) have been extensively studied, uncovering potential molecular mechanisms involving a series of biological processes. Significantly, multi-omics strategies have been launched to provide multi-angle views of complex biological phenomena, facilitating comprehensive insights into molecular regulatory networks during cell migration. In this review, we describe biomimetic devices developed to explore the migratory behaviors of cells induced by different types of confined microenvironments in vitro. We also discuss the results of multi-omics analysis of intrinsic molecular alterations and critical pathway dysregulations of cell migration under heterogeneous microenvironments, highlighting the significance of physical confinement–triggered intracellular signal transduction in order to regulate cellular behaviors. Finally, we discuss both the challenges and promise of mechanistic analysis in confinement-induced cell migration, promoting the development of early diagnosis and precision therapeutics.

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Fig. 1
Fig. 2

Reproduced with permission from Liu et al. [7]. Copyright 2015 Elsevier. B A synthetic hydrogel with a random microchannel network. Reproduced with permission from Siemsen et al. [29]. Copyright 2021 John Wiley and Sons. C A collagen-alginate hydrogel-based microchannel. Reproduced with permission from Wang et al. [30]. Copyright 2019 American Chemical Society. D An integrated microchannel-based chip: A, B showed the schematic diagram of the chip and the physical drawing; C showed the luminal endothelial monolayer in the central channel (VE-Cadherin, red; DAPI, blue) and concentration gradient (green) in the side channels. Reproduced with permission from Roberts et al. [31]. Copyright 2016 American Chemical Society

Fig. 3

Reproduced with permission from Ma et al. [36]. Copyright 2018 AIP Publishing. B Proteome analysis for investigating confinement-induced mesenchymal-amoeboid transition during cell migration. Reproduced with permission from Yang et al. [39]. Copyright 2022 American Chemical Society. C Proteomics analysis for identifying the pivotal differentially expression protein, LH1 (left). Gene ontology (GO) analysis of the differentially expression proteins (right). Reproduced with permission from Yang et al. [41]. Copyright 2023 Springer Nature

Fig. 4

Reproduced with permission from Hsia et al. [48]. Copyright 2022 Elsevier. B Metabolic pathway enrichment analysis of 2D and 3D cultured human dermal fibroblasts. Reproduced with permission from Abdelrahman et al. [49]. Copyright 2023 American Chemical Society. C Transcriptomic and proteomic analysis of mesenchymal-amoeboid transition of fibrosarcoma cells in 3D collagen. Reproduced with permission from Cermak et al. [18]. Copyright 2020 Springer Nature. D The expression of ECM-receptor interaction–related integrin genes regulating viability, proliferation, and migration of DSCM-gel-cultured NSPCs, especially high expression of integrin α2, α9, and β1. Reproduced with permission from Xu et al. [50]. Copyright 2021 Elsevier

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References

  1. Franz CM, Jones GE, Ridley AJ. Cell migration in development and disease. Dev Cell. 2002;2(2):153–8.

    Article  CAS  PubMed  Google Scholar 

  2. Auffray C, Fogg D, Garfa M, Elain G, Join-Lambert O, Kayal S, et al. Monitoring of blood vessels and tissues by a population of monocytes with patrolling behavior. Science. 2007;317(5838):666–70.

    Article  ADS  CAS  PubMed  Google Scholar 

  3. Yamada KM, Cukierman E. Modeling tissue morphogenesis and cancer in 3D. Cell. 2007;130(4):601–10.

    Article  CAS  PubMed  Google Scholar 

  4. Sang Y, Wen X, He Y. Single-cell/nanoparticle trajectories reveal two-tier Levy-like interactions across bacterial swarms. View. 2022;3(6):20220047.

    Article  CAS  Google Scholar 

  5. Song Y, Soto J, Chen B, Hoffman T, Zhao W, Zhu N, et al. Transient nuclear deformation primes epigenetic state and promotes cell reprogramming. Nat Mater. 2022;21(10):1191.

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  6. Nader GPDF, Aguera-Gonzalez S, Routet F, Gratia M, Maurin M, Cancila V, et al. Compromised nuclear envelope integrity drives TREX1-dependent DNA damage and tumor cell invasion. Cell. 2021;184(20):5230.

    Article  CAS  PubMed  Google Scholar 

  7. Liu YJ, Le Berre M, Lautenschlaeger F, Maiuri P, Callan-Jones A, Heuze M, et al. Confinement and low adhesion induce fast amoeboid migration of slow mesenchymal cells. Cell. 2015;160(4):659–72.

    Article  CAS  PubMed  Google Scholar 

  8. Moreau HD, Piel M, Voituriez R, Lennon-Dumenil A-M. Integrating physical and molecular insights on immune cell migration. Trends Immunol. 2018;39(8):632–43.

    Article  CAS  PubMed  Google Scholar 

  9. Yamada KM, Sixt M. Mechanisms of 3D cell migration. Nat Rev Mol Cell Biol. 2019;20(12):738–52.

    Article  CAS  PubMed  Google Scholar 

  10. Smith LR, Cho S, Discher DE. Stem cell differentiation is regulated by extracellular matrix mechanics. Physiology. 2018;33(1):16–25.

    Article  PubMed  Google Scholar 

  11. Wang C, Xu N, Yang Y-J, Wu Q-M, Pang D-W, Zhang Z-L. Enhanced directional cell migration induced by vaccinia virus on a microfluidic-based multi-shear cell migration assay platform. Integr Biol. 2017;9(12):903–11.

    Article  CAS  Google Scholar 

  12. Choi Y, Kwon JE, Cho YK. Dendritic cell migration is tuned by mechanical stiffness of the confining space. Cells. 2021;10(12):3362.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Kameritsch P, Renkawitz J. Principles of leukocyte migration strategies. Trends Cell Biol. 2020;30(10):818–32.

    Article  CAS  PubMed  Google Scholar 

  14. Hashimoto M, Tong R, Kohane DS. Microdevices for nanomedicine. Mol Pharm. 2013;10(6):2127–44.

    Article  CAS  PubMed  Google Scholar 

  15. Onal S, Alkaisi MM, Nock V. Microdevice-based mechanical compression on living cells. Iscience. 2022;25(12):105518.

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  16. Chi P-Y, Spuul P, Tseng F-G, Genot E, Chou C-F, Taloni A. Cell migration in microfluidic devices: invadosomes formation in confined environments. In: LaPorta CAM, Zapperi S, editors. Cell migrations: causes and functions. Adv Exp Med Biol. 11462019, 79-103.

  17. Ha Y, Ma X, Li S, Li T, Li Z, Qian Y, et al. Bone microenvironment-mimetic scaffolds with hierarchical microstructure for enhanced vascularization and bone regeneration. Adv Funct Mater. 2022;32(20):2200011.

    Article  CAS  Google Scholar 

  18. Cermak V, Gandalovicova A, Merta L, Harant K, Roesel D, Brabek J. High-throughput transcriptomic and proteomic profiling of mesenchymal-amoeboid transition in 3D collagen. Scientific Data. 2020;7(1):160.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Ni Y, Xie G, Jia W. Metabonomics of human colorectal cancer: new approaches for early diagnosis and biomarker discovery. J Proteome Res. 2014;13(9):3857–70.

    Article  CAS  PubMed  Google Scholar 

  20. Hanna MH, Dalla Gassa A, Mayer G, Zaza G, Brophy PD, Gesualdo L, et al. The nephrologist of tomorrow: towards a kidney-omic future. Ped Nephrol. 2017;32(3):393–404.

    Article  Google Scholar 

  21. de Jong E, Bosco A. Unlocking immune-mediated disease mechanisms with transcriptomics. Biochem Soc Trans. 2021;49(2):705–14.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Karczewski KJ, Snyder MP. Integrative omics for health and disease. Nat Rev Genet. 2018;19(5):299–310.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Rajasundaram D, Selbig J. More effort - more results: recent advances in integrative ‘omics’ data analysis. Curr Opin Plant Biol. 2016;30:57–61.

    Article  CAS  PubMed  Google Scholar 

  24. Misra BB, Langefeld C, Olivier M, Cox LA. Integrated omics: tools, advances and future approaches. J Mol Endocrinol. 2019;62(1):R21–45.

    Article  CAS  Google Scholar 

  25. Liu Y, Li B, Wang Y-J, Fan Z, Du Y, Li B, et al. In situ single-molecule imaging of microRNAs in switchable migrating cells under biomimetic confinement. Analy Chem. 2022;94(9):4030–8.

    Article  CAS  Google Scholar 

  26. Fan Z, Li B, Wang Y-J, Huang X, Li B, Wang S, et al. Spatially resolved single-molecule profiling of microRNAs in migrating cells driven by microconfinement. Chem Sci. 2022;13(37):11197–204.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Li B, Fan Z, Lu Y, Li B, Huang X, Liu Y, et al. Precise spatial imaging of microRNAs distribution from single living cells. Sensors Actuators B: Chem. 2023;378:133132.

    Article  CAS  Google Scholar 

  28. Lee HP, Alisafaei F, Adebawale K, Chang J, Shenoy VB, Chaudhuri O. The nuclear piston activates mechanosensitive ion channels to generate cell migration paths in confining microenvironments. Sci Adv. 2021;7(2):eabd4058.

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  29. Siemsen K, Rajput S, Rasch F, Taheri F, Adelung R, Lammerding J, et al. Tunable 3D hydrogel microchannel networks to study confined mammalian cell migration. Adv Healthcare Mat. 2021;10(23):e2100625.

    Article  Google Scholar 

  30. Wang M, Cheng B, Yang Y, Liu H, Huang G, Han L, et al. Microchannel stiffness and confinement jointly induce the mesenchymal-amoeboid transition of cancer cell migration. Nano Lett. 2019;19(9):5949–58.

    Article  ADS  CAS  PubMed  Google Scholar 

  31. Roberts SA, Waziri AE, Agrawal N. Development of a single-cell migration and extravasation platform through selective surface modification. Anal Chem. 2016;88(5):2770–6.

    Article  CAS  PubMed  Google Scholar 

  32. Bin Mazalan M, Bin Ramlan MA, Shin JH, Ohashi T. Effect of geometric curvature on collective cell migration in tortuous microchannel devices. Micromachines. 2020;11(7):659.

    Article  Google Scholar 

  33. Xu Y, Pang SW. Natural killer cell migration control in microchannels by perturbations and topography. Lab Chip. 2019;19(14):2466–75.

    Article  CAS  PubMed  Google Scholar 

  34. Afthinos A, Bera K, Chen J, Ozcelikkale A, Amitrano A, Choudhury MI, et al. Migration and 3D traction force measurements inside compliant microchannels. Nano Lett. 2022;22(18):7318–27.

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  35. Shao N, Zhou Y, Yao J, Zhang P, Song Y, Zhang K, et al. A bidirectional single-cell migration and retrieval chip for quantitative study of dendritic cell migration. Adv Sci. 2023;10(8):2204544.

    Article  CAS  Google Scholar 

  36. Ma D, Wang R, Chen S, Luo T, Chow Y-T, Sun D. Microfluidic platform for probing cancer cells migration property under periodic mechanical confinement. Biomicrofluidics. 2018;12(2).

  37. Wouters J, Kalender-Atak Z, Minnoye L, Spanier KI, De Waegeneer M, Bravo González-Blas C, et al. Robust gene expression programs underlie recurrent cell states and phenotype switching in melanoma. Nat Cell Biol. 2020;22(8):986–98.

    Article  CAS  PubMed  Google Scholar 

  38. Park CS, Yoshihara H, Gao Q, Qu C, Iacobucci I, Ghate PS, et al. Stromal-induced epithelial-mesenchymal transition induces targetable drug resistance in acute lymphoblastic leukemia. Cell Rep. 2023;42(7):112804.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Yang S, Xiong Y, Du Y, Wang Y-J, Zhang L, Shen F, et al. Ultrasensitive trace sample proteomics unraveled the protein remodeling during mesenchymal–amoeboid transition. Anal Chem. 2021;94(2):768–76.

    Article  PubMed  Google Scholar 

  40. Wang Y-J, Liang H, Liu Y, Bao Q, Yang S, Xu X-X, et al. Lamin A/C and vimentin as a coordinated regulator during amoeboid migration in microscale confined microenvironments. Nano Lett. 2023;23(14):6727–35.

    Article  ADS  CAS  PubMed  Google Scholar 

  41. Yang Z, Zhou L, Si T, Chen S, Liu C, Ng KK, et al. Lysyl hydroxylase LH1 promotes confined migration and metastasis of cancer cells by stabilizing Septin2 to enhance actin network. Molecular Cancer. 2023;22(1):21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Soflaee MH, Kesavan R, Sahu U, Tasdogan A, Villa E, Djabari Z, et al. Purine nucleotide depletion prompts cell migration by stimulating the serine synthesis pathway. Nat Comm. 2022;13(1):2698.

    Article  ADS  CAS  Google Scholar 

  43. Tong Y, Qi Y, Xiong G, Li J, Scott TL, Chen J, et al. The PLOD2/succinate axis regulates the epithelial–mesenchymal plasticity and cancer cell stemness. Proc Nat Acad Sci. 2023;120(20):e2214942120.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Li J, Agarwal E, Bertolini I, Seo JH, Caino MC, Ghosh JC, et al. The mitophagy effector FUNDC1 controls mitochondrial reprogramming and cellular plasticity in cancer cells. Sci signal. 2020;13(642):eaaz8240.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Guak H, Krawczyk CM. Implications of cellular metabolism for immune cell migration. Immunology. 2020;161(3):200–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Crosas-Molist E, Graziani V, Maiques O, Pandya P, Monger J, Samain R, et al. AMPK is a mechano-metabolic sensor linking cell adhesion and mitochondrial dynamics to myosin-dependent cell migration. Nat Comm. 2023;14(1):2740.

    Article  ADS  CAS  Google Scholar 

  47. Wörheide MA, Krumsiek J, Kastenmüller G, Arnold M. Multi-omics integration in biomedical research–a metabolomics-centric review. Anal Chimica Acta. 2021;1141:144–62.

    Article  Google Scholar 

  48. Hsia C-R, McAllister J, Hasan O, Judd J, Lee S, Agrawal R, et al. Confined migration induces heterochromatin formation and alters chromatin accessibility. Iscience. 2022;25(9):10497.

    Article  Google Scholar 

  49. Abdelrahman S, Ge R, Susapto HH, Liu Y, Samkari F, Moretti M, et al. The impact of mechanical cues on the metabolomic and transcriptomic profiles of human dermal fibroblasts cultured in ultrashort self-assembling peptide 3D scaffolds. ACS Nano. 2023;17(15):14508–31.

    Article  CAS  PubMed  Google Scholar 

  50. Xu Y, Zhou J, Liu C, Zhang S, Gao F, Guo W, et al. Understanding the role of tissue-specific decellularized spinal cord matrix hydrogel for neural stem/progenitor cell microenvironment reconstruction and spinal cord injury. Biomaterials. 2021;268:120596.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We thank Michelle Kahmeyer-Gabbe, PhD, from Liwen Bianji (Edanz) for editing the English text of a draft of this manuscript.

Funding

This work was supported by the National Natural Science Foundation of China (Nos. 21934001, 22274026, and 22204022) and China Postdoctoral Science Foundation funded project (2022M720762).

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  1. Jiayin Lu and Xue-Zhu Chen have contributed equally to this work.

Authors and Affiliations

  1. Department of ChemistryState Key Lab of Molecular Engineering of PolymersShanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Shanghai Stomatological HospitalShanghai Xuhui Central Hospital, Zhongshan-Xuhui HospitalFudan University, Shanghai, China

    Jiayin Lu, Xue-Zhu Chen, Yixin Liu, Yan-Jun Liu & Baohong Liu

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  1. Jiayin Lu
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Lu, J., Chen, XZ., Liu, Y. et al. Trends in confinement-induced cell migration and multi-omics analysis. Anal Bioanal Chem 416, 2107–2115 (2024). https://doi.org/10.1007/s00216-023-05109-4

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