Guided cell migration on a graded micropillar substrate

Cell migration is facilitated by the interaction of living cells and their local microenvironment. The local topography is one of the key factors regulating cell migration. Interaction between the surface topography and the cell behaviors is critical to understanding tissue development and regeneration. In this study, a dynamic mask photolithography technique has been utilized to fabricate a surface with graded micropillars. It has been demonstrated that the cells have been successfully guided to migrate from the sparse zone to the dense zone. The cell polarization angle has been characterized in both sparse zone and the dense zone. Compared to the dense zone, the cells in the sparse zone are more aligned along the direction of the micropillar spacing gradient, which enables the guided cell migration. Moreover, the effects of the micropillar spacing gradient, micropillar diameter, and micropillar height have been investigated in terms of the cell migration speed and cell spreading area. Finally, two issues significantly affecting the cell migration have been discussed: trapped cells between the micropillars and cell clusters.

[1]  Yunus Alapan,et al.  Anisotropically Stiff 3D Micropillar Niche Induces Extraordinary Cell Alignment and Elongation , 2016, Advanced healthcare materials.

[2]  H. Huynh,et al.  Human mesenchymal stem cells preferentially migrate toward highly oncogenic human hepatocellular carcinoma cells with activated EpCAM signaling. , 2017, Oncotarget.

[3]  I. Schneider,et al.  Directed cell migration in multi-cue environments. , 2013, Integrative biology : quantitative biosciences from nano to macro.

[4]  Guillaume Jacquemet,et al.  Filopodia in cell adhesion, 3D migration and cancer cell invasion. , 2015, Current opinion in cell biology.

[5]  Geoffrey W. Stevens,et al.  Cell migration and proliferation during monolayer formation and wound healing , 2009 .

[6]  J. McCarthy,et al.  Laminin and fibronectin promote the haptotactic migration of B16 mouse melanoma cells in vitro , 1984, The Journal of cell biology.

[7]  K. Painter.  Modelling cell migration strategies in the extracellular matrix , 2009, Journal of mathematical biology.

[8]  Kenneth M. Yamada,et al.  One-dimensional topography underlies three-dimensional fibrillar cell migration , 2009, The Journal of cell biology.

[9]  David A. Weitz,et al.  Physical forces during collective cell migration , 2009 .

[10]  G. Danuser,et al.  Two Distinct Actin Networks Drive the Protrusion of Migrating Cells , 2004, Science.

[11]  David Beebe,et al.  An arrayed high-content chemotaxis assay for patient diagnosis. , 2010, Integrative biology : quantitative biosciences from nano to macro.

[12]  P. Mallon,et al.  Surface studies of corona treated polydimethylsiloxane‐block‐polystyrene hybrid copolymer films , 2008 .

[13]  Pascal Silberzan,et al.  Is the mechanical activity of epithelial cells controlled by deformations or forces? , 2005, Biophysical journal.

[14]  Masayuki Yamato,et al.  On-chip cell migration assay using microfluidic channels. , 2007, Biomaterials.

[15]  Kshitiz Gupta,et al.  Mechanosensitivity of fibroblast cell shape and movement to anisotropic substratum topography gradients. , 2009, Biomaterials.

[16]  Changxue Xu,et al.  Biofabrication of 3D cell-encapsulated tubular constructs using dynamic optical projection stereolithography , 2019, Journal of Materials Science: Materials in Medicine.

[17]  Tony J Collins,et al.  ImageJ for microscopy. , 2007, BioTechniques.

[18]  P. Rørth,et al.  Collective cell migration. , 2009, Annual review of cell and developmental biology.

[19]  Min Zhao,et al.  Guided Migration of Neural Stem Cells Derived from Human Embryonic Stem Cells by an Electric Field , 2012, Stem cells.

[20]  Kevin J Luebke,et al.  Correlation of anisotropic cell behaviors with topographic aspect ratio. , 2009, Biomaterials.

[21]  T. Wight,et al.  Microgrooved fibrillar collagen membranes as scaffolds for cell support and alignment. , 2005, Biomaterials.

[22]  Changxue Xu,et al.  Effects of Encapsulated Cells on the Physical–Mechanical Properties and Microstructure of Gelatin Methacrylate Hydrogels , 2019, International journal of molecular sciences.

[23]  Changxue Xu,et al.  Effects of printing conditions on cell distribution within microspheres during inkjet-based bioprinting , 2019, AIP Advances.

[24]  Wei Liu,et al.  Tissue engineering of cartilage with the use of chitosan-gelatin complex scaffolds. , 2004, Journal of biomedical materials research. Part B, Applied biomaterials.

[25]  Dukjin Kang,et al.  Effect of fibroblast co-culture on the proliferation, viability and drug response of colon cancer cells , 2018, Oncology letters.

[26]  Xingyu Jiang,et al.  Patterning mammalian cells for modeling three types of naturally occurring cell-cell interactions. , 2009, Angewandte Chemie.

[27]  Kevin J Painter,et al.  Continuous Models for Cell Migration in Tissues and Applications to Cell Sorting via Differential Chemotaxis , 2009, Bulletin of mathematical biology.

[28]  Marion Ghibaudo,et al.  Traction forces and rigidity sensing regulate cell functions , 2008 .

[29]  S. Pang,et al.  Cell migration on microposts with surface coating and confinement , 2018, Bioscience reports.

[30]  Jianping Fu,et al.  Assaying stem cell mechanobiology on microfabricated elastomeric substrates with geometrically modulated rigidity , 2011, Nature Protocols.

[31]  M. Sticherling,et al.  Bioactive interleukin-8 is expressed in wounds and enhances wound healing. , 2000, The Journal of surgical research.

[32]  Anthony Atala,et al.  A 3D bioprinted complex structure for engineering the muscle–tendon unit , 2015, Biofabrication.

[33]  J. Hubbell,et al.  Mechanisms of 3-D migration and matrix remodeling of fibroblasts within artificial ECMs. , 2007, Acta biomaterialia.

[34]  B. Ladoux,et al.  Fabrication of adjacent micropillar arrays with different heights for cell studies , 2016 .

[35]  Maria E. Mycielska,et al.  Cellular mechanisms of direct-current electric field effects: galvanotaxis and metastatic disease , 2004, Journal of Cell Science.

[36]  M. Dembo,et al.  Cell movement is guided by the rigidity of the substrate. , 2000, Biophysical journal.

[37]  S. Kornbluth,et al.  The Trim39 ubiquitin ligase inhibits APC/CCdh1-mediated degradation of the Bax activator MOAP-1. , 2012, The Journal of cell biology.

[38]  D. Bodas,et al.  Hydrophilization and hydrophobic recovery of PDMS by oxygen plasma and chemical treatment—An SEM investigation , 2007 .

[39]  M. Kwak,et al.  Directed migration of cancer cells by the graded texture of the underlying matrix , 2016, Nature Materials.

[40]  G. Borisy,et al.  Cell Migration: Integrating Signals from Front to Back , 2003, Science.

[41]  N. Sniadecki,et al.  Micropost arrays for measuring stem cell-derived cardiomyocyte contractility. , 2016, Methods.

[42]  Shelly R. Peyton,et al.  Biomechanical Microenvironment Regulates Fusogenicity of Breast Cancer Cells. , 2019, ACS biomaterials science & engineering.

[43]  A. Levchenko,et al.  Topotaxis: A New Mechanism of Directed Cell Migration in Topographic ECM Gradients. , 2018, Biophysical journal.

[44]  P. Searson,et al.  The Influence of Electric Field and Confinement on Cell Motility , 2013, PloS one.

[45]  P. Devreotes,et al.  Eukaryotic Chemotaxis: Distinctions between Directional Sensing and Polarization* , 2003, Journal of Biological Chemistry.

[46]  D. Irvine,et al.  Directed cell migration via chemoattractants released from degradable microspheres. , 2005, Biomaterials.

[47]  A. Mogilner,et al.  Collective cell migration has distinct directionality and speed dynamics , 2017, Cellular and Molecular Life Sciences.

[48]  Huaping Tan,et al.  Gradient biomaterials and their influences on cell migration , 2012, Interface Focus.

[49]  Andre Levchenko,et al.  Matrix nanotopography as a regulator of cell function , 2012, The Journal of cell biology.

[50]  B. Geiger,et al.  Allicin inhibits cell polarization, migration and division via its direct effect on microtubules. , 2007, Cell motility and the cytoskeleton.

[51]  V. Vogel,et al.  The role of filopodia in the recognition of nanotopographies , 2013, Scientific Reports.