Micropatterning-based geometric cell confinement provides novel templates for investigating cellular function and fate. Cell size, shape, and degree of connectivity among cells can be systematically manipulated using micropatterning, allowing for the studies of the effects of patterned cell geometries on cell behavior. Cells conformed to micropatterns develop unique intracellular architectures and signaling activities, regulating cell proliferation, migration, survival/apoptosis, commitment, and differentiation. Cell patterning size controls cell survival and apoptosis and stem cell fate via cytoskeletal tension signaling such as RhoA-ROCK. Cell patterning shape affects cell growth and migration via altered cellular polarity and Rac1 signaling. Modulation of cell-cell interconnectivity via micropatterning affects proliferation and differentiation via regulating the expression of cell-cell interaction molecules such as cadherin. Systematic assessment of cell function and fate using micropatterned cells will shed new insights for understanding the mechanisms in cell and molecular biology studies and for the control of cell behavior in biomedical applications.
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Wang N, Ingber DE. Control of cytoskeletal mechanics by extracellular matrix, cell shape, and mechanical tension. J Bioph. 1994; 66(6):2181–2189.
Corey JM, Feldman EL. Substrate patterning: An emerging technology for the study of neuronal behavior. Exp Neurol. 2003; 184Suppl 1:S89–S96.
Chen CS, Mrksich M, Huang S, Whitesides GM, Ingber DE. Geometric control of cell life and death. Science. 1997; 276(5317):1425–1428.
Chen CS, Mrksich M, Huang S, Whitesides GM, Ingber DE. Micropatterned surfaces for control of cell shape, position, and function. Biotech Prog. 1998; 14(3):356–363.
Yang IH, Co CC, Ho CC. Alteration of human neuroblastoma cell morphology and neurite extension with micropatterns. Biomaterials. 2005; 26(33):6599–609.
Frimat JP, Sisnaiske J, Subbiah S, Menne H, Godoy P, Lampen P, Leist M, Franzke J, Hengstler JG, van Thriel C, West J. The network formation assay: A spatially standardized neurite outgrowth analytical display for neurotoxicity screening. Lab Chip. 2010; 10(6):701–709.
Jiang X, Ferrigno R, Mrksich M, Whitesides GM. Electrochemical desorption of self-assembled monolayers noninvasively releases patterned cells from geometrical confinements. J Am Chem Soc. 2003; 125(9):2366–2367.
Kushiro K, Chang S, Asthagiri AR. Reprogramming directional cell motility by tuning micropattern features and cellular signals. Advan Mater. 2010; 22(40):4516–4519.
Rosenthal A, Macdonald A, Voldman J. Cell patterning chip for controlling the stem cell microenvironment. Biomaterials. 2007; 28(21):3208–3216.
Thery M. Micropatterning as a tool to decipher cell morphogenesis and functions. J Cell Sci. 2010; 123(24):4201–13.
McBeath R, Pirone DM, Nelson CM, Bhadriraju K, Chen CS. Cell shape, cytoskeletal tension, and RhoA regulate stem cell lineage commitment. Dev Cell. 2004; 6(4):483–495.
Lim JY, Donahue HJ. Cell sensing and response to micro- and nanostructured surfaces produced by chemical and topographic patterning. Tissue Eng. 2007; 13(8):1879–1891.
Ostuni E, Whitesides GM, Ingber DE, Chen CS. Using selfassembled monolayers to pattern ECM proteins and cells on substrates. Method Mol Biol. 2009; 522:183–194.
Lussi JW, Michel R, Reviakine I, Falconnet D, Goessl A, Csucs G, Hubbell JA, Textor M. A novel generic platform for chemical patterning of surfaces. Prog Surf Sci. 2004; 76:55–69.
Falconnet D, Koenig A, Assi T, Textor M. A combined photolithographic and molecular-assembly approach to produce functional micropatterns for applications in the biosciences. Adv Funct Mater. 2004; 14:749–756.
Lahann J, Mitragotri S, Tran TN, Kaido H, Sundaram J, Choi IS, Hoffer S, Somorjai GA, Langer R. A reversibly switching surface. Science. 2003; 299(5605):371–374.
Kidambi S, Lee I, Chan C. Patterned co-culture of neurons and astrocytes on polyelectrolyte multilayer films for studying astrocyte mediated oxidative stress in neurons. Adv Funct Mater. 2008; 18:294–301.
Folch A, Jo BH, Hurtado O, Beebe DJ, Toner M. Microfabricated elastomeric stencils for micropatterning cell cultures. J Biomed Mater Res. 2000; 52(2):346–353.
Rettig JR, Folch A. Large-scale single-cell trapping and imaging using microwell arrays. Anal Chem. 2005; 77(17):5628–34.
Shi J, Ahmed D, Mao X, Lin SC, Lawit A, Huang TJ. Acoustic tweezers: patterning cells and microparticles using standing surface acoustic waves (SSAW). Lab Chip. 2009; 9(20):2890–2895.
Albrecht DR, Underhill GH, Wassermann TB, Sah RL, Bhatia SN. Probing the role of multicellular organization in threedimensional microenvironments. Nat Methods. 2006; 3(5):369–375.
Gray DS, Liu WF, Shen CJ, Bhadriraju K, Nelson CM, Chen CS. Engineering amount of cell-cell contact demonstrates biphasic proliferative regulation through RhoA and the actin cytoskeleton. Exp Cell Res. 2008; 314(15):2846–2854.
Buyukhatipoglu K, Chang R, Sun W, Clyne AM. Bioprinted nanoparticles for tissue engineering applications. Tissue Eng Part C Meth. 2010; 16(4):631–642.
Buzanska L, Zychowicz M, Ruiz A, Ceriotti L, Coecke S, Rauscher H, Sobanski T, Whelan M, Domanska-Janik K, Colpo P, Rossi F. Neural stem cells from human cord blood on bioengineered surfaces-novel approach to multiparameter biotests. Toxicol. 2010; 270(1):35–42.
El-Amraoui A, Petit C. Cadherins as targets for genetic diseases. Cold Spring Harb Perspect Biol. 2010; 2(1):a003095.
Chen CS, Alonso JL, Ostuni E, Whitesides GM, Ingber DE. Cell shape provides global control of focal adhesion assembly. Biochem Biophys Res Commun. 2003; 307(2):355–361.
Watt FM, Jordan PW, O’Neill CH. Cell shape controls terminal differentiation of human epidermal keratinocytes. P Natl Acad Sci USA. 1988; 85(15):5576–5580.
Ingber D. Extracellular matrix and cell shape: Potential control points for inhibition of angiogenesis. J Cell Biochem. 1991; 47(3):236–41.
Lim JY, Taylor AF, Li Z, Vogler EA, Donahue HJ. Integrin expression and osteopontin regulation in human fetal osteoblastic cells mediated by substratum surface characteristics. Tissue Eng. 2005; 11(1–2):19–29.
Lim JY, Shaughnessy MC, Zhou Z, Noh H, Vogler EA, Donahue HJ. Surface energy effects on osteoblast spatial growth and mineralization. Biomaterials. 2008; 29(12):1776–1784.
Song W, Lu H, Kawazoe N, Chen G. Adipogenic differentiation of individual mesenchymal stem cell on different geometric micropatterns. Langmuir. 2011; 27(10):6155–162.
Gao L, McBeath R, Chen CS. Stem cell shape regulates a chondrogenic versus myogenic fate through Rac1 and Ncadherin. Stem Cells. 2010; 28(3):564–572.
Thomas CH, Collier JH, Sfeir CS, Healy KE. Engineering gene expression and protein synthesis by modulation of nuclear shape. P Natl Acad Sci USA. 2002; 99(4):1972–1977.
Jiang X, Bruzewicz DA, Wong AP, Piel M, Whitesides GM. Directing cell migration with asymmetric micropatterns. P Natl Acad Sci USA. 2005; 102(4):975–978.
Kumar G, Ho CC, Co CC. Guiding cell migration using one-way micropattern arrays. Adv Mater. 2007; 19:1084–90.
Nelson CM, Jean RP, Tan JL, Liu WF, Sniadecki NJ, Spector AA, Chen CS. Emergent patterns of growth controlled by multicellular form and mechanics. P Natl Acad Sci USA. 2005; 102(33):11594–11599.
Nishimura T, Takeichi M. Remodeling of the adherens junctions during morphogenesis. Curr Top Dev Biol. 2009; 89:33–54.
Stains JP, Civitelli R. Cell-to-cell interactions in bone. Biochem Bioph Res Co. 2005; 328(3):721–727.
Zhang Y, Paul EM, Sathyendra V, Davison A, Sharkey N, Bronson S, Srinivasan S, Gross TS, Donahue HJ. Enhanced osteoclastic resorption and responsiveness to mechanical load in gap junction deficient bone. PLoS One. 2011; 6(8):e23516.
Bloemen V, Schoenmaker T, de Vries TJ, Everts V. Direct cellcell contact between periodontal ligament fibroblasts and osteoclast precursors synergistically increases the expression of genes related to osteoclastogenesis. J Cell Physiol. 2010; 222(3):565–573.
Charest JL, Jennings JM, King WP, Kowalczyk AP, Garcia AJ. Cadherin-mediated cell-cell contact regulates keratinocyte differentiation. J Invest Dermatol. 2009; 129(3):564–572.
Cukierman E, Pankov R, Stevens DR, Yamada KM. Taking cell-matrix adhesions to the third dimension. Science. 2001; 294(5547):1708–12.
Xu Y, Yao H, Wang L, Xing W, Cheng J. The construction of an individually addressable cell array for selective patterning and electroporation. Lab Chip. 2011; 11(14):2417–2423.
Fedorovich NE, Alblas J, Hennink WE, Oner FC, Dhert WJ. Organ printing: the future of bone regeneration? Trends Biotechnol. 2011; 29(12):601–606.
Gruene M, Pflaum M, Hess C, Diamantouros S, Schlie S, Deiwick A, Koch L, Wilhelmi M, Jockenhoevel S, Haverich A, Chichkov B. Laser printing of three-dimensional multicellular arrays for studies of cell-cell and cell-environment interactions. Tissue Eng Part C Method. 2011; 17(10):973–982.
Hanson Shepherd JN, Parker ST, Shepherd RF, Gillette MU, Lewis JA, Nuzzo RG. 3D Microperiodic Hydrogel Scaffolds for Robust Neuronal Cultures. Adv Funct Mater. 2011; 21(1):47–54.
Park JY, Takayama S, Lee SH. Regulating microenvironmental stimuli for stem cells and cancer cells using microsystems. Integr Biol (Camb). 2010; 2(5–6):229–240.
Kim S, Kim HJ, Jeon NL. Biological applications of microfluidic gradient devices. Integr Biol (Camb). 2010; 2(11–12):584–603.
Moraes C, Sun Y, Simmons CA. (Micro)managing the mechanical microenvironment. Integr Biol (Camb). 2011; 3(10):959–971.
Tavana H, Jovic A, Mosadegh B, Lee QY, Liu X, Luker KE, Luker GD, Weiss SJ, Takayama S. Nanolitre liquid patterning in aqueous environments for spatially defined reagent delivery to mammalian cells. Nat Mater. 2009; 8(9):736–741.
Poudel and Menter contributed equally.
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Poudel, I., Menter, D.E. & Lim, J.Y. Directing cell function and fate via micropatterning: Role of cell patterning size, shape, and interconnectivity. Biomed. Eng. Lett. 2, 38–45 (2012). https://doi.org/10.1007/s13534-012-0045-z
- Geometric confinement
- Cell size