Microfabricated Devices for Studying Cellular Biomechanics and Mechanobiology

Studies in Mechanobiology, Tissue Engineering and Biomaterials

Volumn 4, Issue , 2011, Pages 145-175

  Moraes, Christopher ^a,b   Sun, Yu ^a,b   Simmons, Craig A ^a,b  

^a UNIVERSITY OF TORONTO   (Canada)

^b UNIVERSITY OF TORONTO   (Canada)

Author keywords

Cytoskeletal Tension; Microfluidic Channel; Micropipette Aspiration; Parallel Plate Flow Chamber; Traction Force

Indexed keywords

EID: 85070841304     PISSN: 18682006     EISSN: 18682014     Source Type: Book Series    
DOI: 10.1007/8415_2010_24     Document Type: Chapter

References (186)

1. Ridley, A.J., Hall, A.: The small Gtp-binding protein Rho regulates the assembly of focal adhesions and actin stress fibers in response to growth-factors. Cell 70, 389–399 (1992)
2. Smith, P.G., Deng, L.H., Fredberg, J.J., et al.: Mechanical strain increases cell stiffness through cytoskeletal filament reorganization. Am. J. Physiol. Lung Cell. Mol. Physiol. 285, L456–L463 (2003)
3. Chen C.S., Tan J., Tien J.: Mechanotransduction at cell-matrix and cell-cell contacts. Annu Rev Biomed Eng. 6, 275–302 (2004).
4. Darling, E.M., Topel, M., Zauscher, S., et al.: Viscoelastic properties of human mesenchymally-derived stem cells and primary osteoblasts, chondrocytes, and adipocytes. J. Biomech. 41, 454–464 (2008)
5. Huang, H.D., Kamm, R.D., Lee, R.T.: Cell mechanics and mechanotransduction: pathways, probes, and physiology. Am. J. Physiol. Cell Physiol. 287, C1–C11 (2004)
6. Titushkin, I., Cho, M.: Modulation of cellular mechanics during osteogenic differentiation of human mesenchymal stem cells. Biophys. J. 93, 3693–3702 (2007)
7. Janmey, P.A., McCulloch, C.A.: Cell mechanics: integrating cell responses to mechanical stimuli. Annu. Rev. Biomed. Eng. 9, 1–34 (2007)
8. Fletcher, D.A., Mullins, R.D.: Cell mechanics and the cytoskeleton. Nature 463, 485–492 (2010)
9. Treiser, M.D., Yang, E.H., Gordonov, S., et al.: Cytoskeleton-based forecasting of stem cell lineage fates. Proc. Natl. Acad. Sci. USA 107, 610–615 (2010)
10. Hsieh, M.H., Nguyen, H.T.: Molecular mechanism of apoptosis induced by mechanical forces. Int. Rev. Cytol. 245, 45–90 (2005)
11. McBeath, R., Pirone, D.M., Nelson, C.M., et al.: Cell shape, cytoskeletal tension, and RhoA regulate stem cell lineage commitment. Dev. Cell. 6, 483–495 (2004)
12. Ridley, A.J., Schwartz, M.A., Burridge, K., et al.: Cell migration: integrating signals from front to back. Science 302, 1704–1709 (2003)
13. Kaibuchi, K., Kuroda, S., Amano, M.: Regulation of the cytoskeleton and cell adhesion by the Rho family GTPases in mammalian cells. Annu. Rev. Biochem. 68, 459–486 (1999)
14. Ingber, D.E.: Cellular mechanotransduction: putting all the pieces together again. FASEB J. 20, 811–827 (2006)
15. Orr, A.W., Helmke,B.P., Blackman, B.R., et al.: Mechanisms of mechanotransduction. Dev Cell. 10, 11–20 (2006)
16. Ward, K.A., Li, W.I., Zimmer, S., et al.: Viscoelastic properties of transformed cells: role in tumor cell progression and metastasis formation. Biorheology. 28, 301–313 (1991)
17. Suresh, S.: Biomechanics and biophysics of cancer cells. Acta Biomater. 3, 413–438 (2007)
18. Suresh, S., Spatz, J., Mills, J.P. et al.: Connections between single-cell biomechanics and human disease states: gastrointestinal cancer and malaria. Acta Biomater. 1, 15–30 (2005)
19. Lee, G.Y, Lim, C.T.: Biomechanics approaches to studying human diseases. Trends Biotechnol. 25, 111–118 (2007)
20. Higgins, J.M., Eddington, D.T., Bhatia, S.N., et al.: Sickle cell vasoocclusion and rescue in a microfluidic device. Proc. Natl. Acad. Sci. USA 104, 20496–20500 (2007)
21. Merryman, W.D., Engler, A.J.: Innovations in cell mechanobiology. J. Biomech. 43, 1–1 (2010)
22. Stoltz, J.F., Wang, X.: From biomechanics to mechanobiology. Biorheology 39, 5–10 (2002)
23. Guck J., Schinkinger S., Lincoln B., et al.: Optical deformability as an inherent cell marker for testing malignant transformation and metastatic competence. Biophys. J. 88, 3689–3698 (2005)
24. Desai, R.A., Gao, L., Raghavan, S., et al.: Cell polarity triggered by cell-cell adhesion via E-cadherin. J. Cell Sci. 122, 905–911 (2009)
25. Ingber, D.E.: Mechanobiology and diseases of mechanotransduction. Ann. Med. 35, 564– 577 (2003)
26. Wozniak, M.A., Chen, C.S.: Mechanotransduction in development: a growing role for contractility. Nat. Rev. Mol. Cell Biol. 10, 34–43 (2009)
27. van der Meulen M.C., Huiskes, R.: Why mechanobiology? A survey article. J. Biomech. 35, 401–414 (2002)
28. Wang, J.H., Thampatty, B.P.: An introductory review of cell mechanobiology. Biomech. Model Mechanobiol. 5, 1–16 (2006)
29. Bao, G., Suresh, S.: Cell and molecular mechanics of biological materials. Nat. Mater. 2, 715–725 (2003)
30. Makale M.: Cellular mechanobiology and cancer metastasis. Birth Defects Res. C Embryo Today. 81, 329–343 (2007)
31. Jaalouk, D.E., Lammerding, J.: Mechanotransduction gone awry. Nat. Rev. Mol. Cell Biol. 10, 63–73 (2009)
32. Ingber D.E.: Mechanical control of tissue morphogenesis during embryological development. Int. J. Dev. Biol. 50, 255–266 (2006)
33. Chen, J.H., Liu, C., You, L., et al.: Boning up on Wolff’s Law: mechanical regulation of the cells that make and maintain bone. J. Biomech. 43, 108–118 (2010)
34. Wang, J.H.: Mechanobiology of tendon. J. Biomech. 39, 1563–1582 (2006)
35. Butcher, J.T., Simmons, C.A., Warnock, J.N.: Mechanobiology of the aortic heart valve. J. Heart Valve Dis. 17, 62–73 (2008)
36. Setton, L.A., Chen, J.: Cell mechanics and mechanobiology in the intervertebral disc. Spine 29, 2710–2723 (2004)
37. Lammi, M.J.: Current perspectives on cartilage and chondrocyte mechanobiology. Biorheology 41, 593–596 (2004)
38. Huselstein, C., Netter, P., de Isla, N., et al.: Mechanobiology, chondrocyte and cartilage. Biomed. Mater. Eng. 18, 213–220 (2008)
39. Loh, O., Vaziri, A., Espinosa, H.D.: The potential of MEMS for advancing experiments and modeling in cell mechanics. Exp. Mech. 49, 105–124 (2009)
40. Kim, D.H., Wong, P.K., Park J., et al.: Microengineered platforms for cell mechanobiology. Annu. Rev. Biomed. Eng. 11, 203––233 (2009)
41. Vanapalli, S.A., Duits, M.H., Mugele, F.: Microfluidics as a functional tool for cell mechanics. Biomicrofluidics 3, 12006 (2009)
42. Sims, C.E., Allbritton, N.L.: Analysis of single mammalian cells on-chip. Lab Chip 7, 423– 440 (2007)
43. Ferrell, J.E., Jr., Machleder, E.M.: The biochemical basis of an all-or-none cell fate switch in Xenopus oocytes. Science 280, 895–898 (1998)
44. Ethier, C.R., Simmons, C.A.: Introductory Biomechanics: from Cells to Organisms. Cambridge University Press, London (2007)
45. Hoffman, B.D., Crocker, J.C.: Cell mechanics: dissecting the physical responses of cells to force. Annu. Rev. Biomed. Eng. 11, 259–288 (2009)
46. Lim, C.T., Zhou, E.H., Quek, S.T.: Mechanical models for living cells—a review. J. Biomech. 39:195–216 (2006)
47. Pelling, A.E., Horton, M.A.: An historical perspective on cell mechanics. Pflugers Arch. 456, 3–12 (2008)
48. Lim, C.T., Zhou, E.H., Li, A., et al.: Experimental techniques for single cell and single molecule biomechanics. Mater. Sci. Eng. C Biomim. Supramol. Syst. 26, 1278–1288 (2006)
49. Thoumine, O., Ott, A., Cardoso, O., et al.: Microplates: a new tool for manipulation and mechanical perturbation of individual cells. J. Biochem. Biophys. Methods 39, 47–62 (1999)
50. Peeters, E.A., Bouten, C.V., Oomens, C.W., et al.: Monitoring the biomechanical response of individual cells under compression: a new compression device. Med. Biol. Eng. Comput. 41, 498–503 (2003)
51. Guck, J., Ananthakrishnan, R., Mahmood, H., et al.: The optical stretcher: a novel laser tool to micromanipulate cells. Biophys. J. 81, 767–784 (2001)
52. Mitchison, J.M., Swann, M.M.: The mechanical properties of the cell surface.1. The cell elastimeter. J. Exp. Biol. 31, 443–460 (1954)
53. Hochmuth, R.M.: Micropipette aspiration of living cells. J. Biomech. 33, 15–22 (2000)
54. Wang, N., Ingber, D.E.: Probing transmembrane mechanical coupling and cytomechanics using magnetic twisting cytometry. Biochem. Cell Biol. 73, 327–335 (1995)
55. Bausch, A.R., Ziemann, F., Boulbitch, A.A., et al.: Local measurements of viscoelastic parameters of adherent cell surfaces by magnetic bead microrheometry. Biophys. J. 75, 2038–2049 (1998)
56. Li, J., Dao, M., Lim, C.T. et al.: Spectrin-level modeling of the cytoskeleton and optical tweezers stretching of the erythrocyte. Biophys. J. 88, 3707–3719 (2005)
57. Mills, J.P., Qie, L., Dao, M., et al.: Nonlinear elastic and viscoelastic deformation of the human red blood cell with optical tweezers. Mech. Chem. Biosyst. 1, 169–180 (2004)
58. Costa, K.D.: Single-cell elastography: probing for disease with the atomic force microscope. Dis Markers. 19, 139–154 (2003)
59. de Vries, A.H., Krenn, B.E,, van Driel, R., et al.: Micro magnetic tweezers for nanomanipulation inside live cells. Biophys. J. 88, 2137–2144 (2005)
60. Panchawagh, H.V., Serrell, D., Finch, D.S., et al.: Design and characterization of a BioMEMS device for in vitro mechanical stimulation of single adherent cells. Micro-Electro-Mechanical Syst. 7, 19–25 (2005)
61. Scuor, N., Gallina, P., Panchawagh, H.V, et al.: Design of a novel MEMS platform for the biaxial stimulation of living cells. Biomed. Microdevices 8, 239–246 (2006)
62. Zhang, W.Y., Gnerlich, M., Paly, J.J., et al.: A polymer V-shaped electrothermal actuator array for biological applications. J. Micromech. Microeng. 18, 075020 (2008)
63. Serrell, D.B., Law, J., Slifka, A.J., et al.: A uniaxial bioMEMS device for imaging single cell response during quantitative force-displacement measurements. Biomed. Microdevices 10, 883–889 (2008)
64. Voldman, J.: Electrical forces for microscale cell manipulation. Annu. Rev. Biomed. Eng. 8, 425–454 (2006)
65. Mukundan, V., Pruitt, B.L.: MEMS electrostatic actuation in conducting biological media. J. Microelectromech. Syst. 18, 405–413 (2009)
66. Waugh, R., Evans, E.A.: Thermoelasticity of red blood cell membrane. Biophys. J. 26, 115– 131 (1979)
67. Engelhardt, H., Gaub, H., Sackmann, E.: Viscoelastic properties of erythrocyte membranes in high-frequency electric fields. Nature. 307, 378–380 (1984)
68. Korlach, J., Reichle, C., Muller, T. et al.: Trapping, deformation, and rotation of giant unilamellar vesicles in octode dielectrophoretic field cages. Biophys. J. 89, 554–562 (2005)
69. Wong, P.K., Tan, W., Ho, C.M.: Cell relaxation after electrodeformation: effect of latrunculin A on cytoskeletal actin. J. Biomech. 38, 529–535 (2005)
70. Kim, K., Cheng, J., Liu, Q. et al.: Investigation of mechanical properties of soft hydrogel microcapsules in relation to protein delivery using a MEMS force sensor. J. Biomed. Mater. Res. Part A 92A, 103–113 (2010)
71. Serrell, D.B., Oreskovic, T.L., Slifka, A.J., et al.: A uniaxial bioMEMS device for quantitative force-displacement measurements. Biomed. Microdevices 9, 267–275 (2007)
72. Yang, S., Saif, T.: Reversible and repeatable linear local cell force response under large stretches. Exp. Cell Res. 305, 42–50 (2005)
73. Yang, S., Saif, M.T.: Force response and actin remodeling (agglomeration) in fibroblasts due to lateral indentation. Acta Biomater. 3, 77–87 (2007)
74. Yang, S., Saif, M.T.A.: Microfabricated force sensors and their applications in the study of cell mechanical response. Exp. Mech. 49, 135–151 (2009)
75. Falconnet, D., Csucs, G., Grandin, H.M., et al.: Surface engineering approaches to micropattern surfaces for cell-based assays. Biomaterials 27, 3044–3063 (2006)
76. Fink, J., Thery, M., Azioune, A., et al.: Comparative study and improvement of current cell micro-patterning techniques. Lab Chip 7, 672–680 (2007)
77. Lu, Z., Moraes, C., Zhao, Y., et al.: A micromanipulation system for single cell deposition. In: IEEE International Conference on Robotics and Automation (ICRA2010), Alaska, 3–8 May 2010
78. Chen, N.N., Tucker, C., Engel, J.M., et al.: Design and characterization of artificial haircell sensor for flow sensing with ultrahigh velocity and angular sensitivity. J. Microelectromech. Syst. 16, 999–1014 (2007)
79. Liu, C.: Micromachined biomimetic artificial haircell sensors. Bioinspir. Biomim. 2, S162– S169 (2007)
80. Sasoglu, F.M., Bohl, A.J., Layton, B.E.: Design and microfabrication of a high-aspect-ratio PDMS microbeam array for parallel nanonewton force measurement and protein printing. J. Micromech. Microeng. 17, 623–632 (2007)
81. Sasoglu, F.M., Bohl, A.J., Allen, K.B., et al.: Parallel force measurement with a polymeric microbeam array using an optical microscope and micromanipulator. Comput. Methods Programs Biomed. 93, 1–8 (2009)
82. Liu, X.Y., Fernandes, R., Jurisicova, A., et al.: In situ mechanical characterization of mouse oocytes. Lab Chip 10, 2154–2161 (2010)
83. Lincoln, B., Schinkinger, S., Travis, K., et al.: Reconfigurable microfluidic integration of a dual-beam laser trap with biomedical applications. Biomed. Microdevices 9, 703–710 (2007)
84. Rosenbluth, M.J., Lam, W.A., Fletcher, D.A.: Force microscopy of nonadherent cells: a comparison of leukemia cell deformability. Biophys. J. 90, 2994–3003 (2006)
85. Unger, M.A., Chou, H.P., Thorsen, T., et al.: Monolithic microfabricated valves and pumps by multilayer soft lithography. Science. 288, 113–116 (2000)
86. Kim, Y.C., Kang, J.H., Park, S.J., et al.: Microfluidic biomechanical device for compressive cell stimulation and lysis. Sens. Actuators B Chem. 128, 108–116 (2007)
87. Hohne, D.N., Younger, J.G., Solomon, M.J.: Flexible microfluidic device for mechanical property characterization of soft viscoelastic solids such as bacterial biofilms. Langmuir 25, 7743–7751 (2009)
88. Kim, Y.C., Park, S.J., Park, J.K.: Biomechanical analysis of cancerous and normal cells based on bulge generation in a microfluidic device. Analyst 133, 1432–1439 (2008)
89. Moraes, C., Wyss, K., Brisson, E., et al.: An Undergraduate lab (on-a-chip): probing single cell mechanics on a microfluidic platform. Cell. Mol. Bioeng. (2010). doi:10.1007/s12195-010-0124-0.
90. Moraes, C., Tong, J.H., Liu, X.Y., et al.: Parallel micropipette aspirator arrays for high-throughput mechanical characterization of biological cells. In: Proceedings of the Micro Total Analysis Systems Conference, pp. 751–753 (2007)
91. Sagvolden, G., Giaever, I., Pettersen, E.O., et al.: Cell adhesion force microscopy. Proc. Natl. Acad. Sci. USA 96, 471–476 (1999)
92. Shao, J.Y., Xu, J.B.: A modified micropipette aspiration technique and its application to tether formation from human neutrophils. J. Biomech. Eng. Trans. ASME 124, 388–396 (2002)
93. Fu, G., Milburn, C., Mwenifumbo, S., et al.: Shear assay measurements of cell adhesion on biomaterials surfaces. Mater. Sci. Eng. C-Biomimetic Supramol. Syst. 29, 1293–1301 (2009)
94. Lu, H., Koo, L.Y., Wang, W.C.M., et al.: Microfluidic shear devices for quantitative analysis of cell adhesion. Anal. Chem. 76, 5257–5264 (2004)
95. Young, E.W.K., Wheeler, A.R., Simmons, C.A.: Matrix-dependent adhesion of vascular and valvular endothelial cells in microfluidic channels. Lab Chip 7, 1759–1766 (2007)
96. Kwon, K.W., Choi, S.S., Lee, S.H., et al.: Label-free, microfluidic separation and enrichment of human breast cancer cells by adhesion difference. Lab Chip 7, 1461–1468 (2007)
97. Couzon, C., Duperray, A., Verdier, C. Critical stresses for cancer cell detachment in microchannels. Eur. Biophys. J. Biophys. Lett. 38, 1035–1047 (2009)
98. Wankhede, S.P., Du, Z.Q., Berg, J.M., et al.: Cell detachment model for an antibody-based microfluidic cancer screening system. Biotechnol. Prog. 22, 1426–1433 (2006)
99. Plouffe, B.D., Radisic, M., Murthy, S.K: Microfluidic depletion of endothelial cells, smooth muscle cells, and fibroblasts from heterogeneous suspensions. Lab Chip 8, 462–472 (2008)
100. Plouffe, B.D., Brown, M.A., Iyer, R.K., et al.: Controlled capture and release of cardiac fibroblasts using peptide-functionalized alginate gels in microfluidic channels. Lab Chip 9, 1507–1510 (2009)
101. Plouffe, B.D., Njoka, D.N., Harris, J., et al.: Peptide-mediated selective adhesion of smooth muscle and endothelial cells in microfluidic shear flow. Langmuir 23, 5050–5055 (2007)
102. Gutierrez, E., Groisman, A.: Quantitative measurements of the strength of adhesion of human neutrophils to a substratum in a microfluidic device. Anal. Chem. 79, 2249–2258 (2007)
103. Harris, A.K., Wild, P., Stopak, D.: Silicone rubber substrata: a new wrinkle in the study of cell locomotion. Science 208, 177–179 (1980)
104. Vanni, S., Lagerholm, B.C., Otey, C., et al.: Internet-based image analysis quantifies contractile behavior of individual fibroblasts inside model tissue. Biophys. J. 84, 2715–2727 (2003)
105. Dembo, M., Oliver, T., Ishihara, A., et al.: Imaging the traction stresses exerted by locomoting cells with the elastic substratum method. Biophys, J. 70, 2008–2022 (1996)
106. Galbraith, C.G., Sheetz, M.P.: A micromachined device provides a new bend on fibroblast traction forces. Proc. Natl. Acad. Sci. USA 94, 9114–9118 (1997)
107. Galbraith, C.G., Sheetz, M.P.: Forces on adhesive contacts affect cell function. Curr. Opin. Cell Biol. 10, 566–571 (1998)
108. Tan, J.L., Tien, J., Pirone, D.M., et al.: Cells lying on a bed of microneedles: an approach to isolate mechanical force. Proc. Natl. Acad. Sci. USA 100, 1484–1489 (2003)
109. Li, B., Xie, L., Starr, Z.C., et al.: Development of micropost force sensor array with culture experiments for determination of cell traction forces. Cell Motil. Cytoskeleton 64, 509–518 (2007)
110. Legant, W.R., Pathak, A., Yang, M.T., et al.: Microfabricated tissue gauges to measure and manipulate forces from 3D microtissues. Proc. Natl. Acad. Sci. USA 106, 10097–10102 (2009)
111. Chen, C.S.: Mechanotransduction—a field pulling together? J. Cell Sci. 121, 3285–3292 (2008)
112. Barbulovic-Nad, I., Lucente, M., Sun, Y. et al.: Bio-microarray fabrication techniques—a review. Crit. Rev. Biotechnol. 26, 237–259 (2006)
113. Schmalenberg, K.E., Buettner, H.M., Uhrich, K.E.: Microcontact printing of proteins on oxygen plasma-activated poly(methyl methacrylate). Biomaterials 25, 1851–1857 (2004)
114. Bernard, A., Renault, J.P., Michel, B., et al.: Microcontact printing of proteins. Adv. Mater. 12, 1067–1070 (2000)
115. Ostuni, E., Kane, R., Chen, C.S., et al.: Patterning mammalian cells using elastomeric membranes. Langmuir 16, 7811–7819 (2000)
116. Langowski, B.A., Uhrich, K.E.: Microscale plasma-initiated patterning (muPIP). Langmuir 21, 10509–10514 (2005)
117. Rhee, S.W., Taylor, A.M., Tu, C.H., et al.: Patterned cell culture inside microfluidic devices. Lab Chip 5, 102–107 (2005)
118. Takayama, S., McDonald, J.C., Ostuni, E., et al.: Patterning cells and their environments using multiple laminar fluid flows in capillary networks. Proc. Natl. Acad. Sci. USA 96, 5545–5548 (1999)
119. Jiang, X., Xu, Q., Dertinger, S.K., et al.: A general method for patterning gradients of biomolecules on surfaces using microfluidic networks. Anal. Chem. 77, 2338–2347 (2005)
120. Yeo, W.S., Yousaf, M.N., Mrksich, M.: Dynamic interfaces between cells and surfaces: electroactive substrates that sequentially release and attach cells. J. Am. Chem. Soc. 125, 14994–14995 (2003)
121. Yeo, W.S., Mrksich, M.: Electroactive self-assembled monolayers that permit orthogonal control over the adhesion of cells to patterned substrates. Langmuir 22, 10816–10820 (2006)
122. Fan, C.Y., Tung, Y.C., Takayama, S., et al.: Electrically programmable surfaces for configurable patterning of cells. Adv. Mater. 20, 1418 (2008)
123. Chen, C.S., Mrksich, M., Huang, S., et al.: Geometric control of cell life and death. Science 276, 1425–1428 (1997)
124. Wang, N., Ostuni, E., Whitesides, G.M., et al.: Micropatterning tractional forces in living cells. Cell Motil Cytoskeleton 52, 97–106 (2002)
125. Parker, K.K., Brock, A.L., Brangwynne, C., et al.: Directional control of lamellipodia extension by constraining cell shape and orienting cell tractional forces. FASEB J. 16, 1195–1204 (2002)
126. Brock, A., Chang, E., Ho, C.C., et al.: Geometric determinants of directional cell motility revealed using microcontact printing. Langmuir 19, 1611–1617 (2003)
127. Jiang, X., Bruzewicz, D.A., Wong, A.P., et al.: Directing cell migration with asymmetric micropatterns. Proc. Natl. Acad. Sci USA 102, 975–978 (2005)
128. Ruiz, S.A., Chen, C.S.: Emergence of patterned stem cell differentiation within multicellular structures. Stem Cells 26, 2921–2927 (2008)
129. Kilian, K.A., Bugarija, B., Lahn, B.T., et al.: Geometric cues for directing the differentiation of mesenchymal stem cells. Proc. Natl. Acad. Sci. USA 107, 4872–4877 (2010)
130. Ochsner, M., Dusseiller, M.R., Grandin, H.M., et al.: Micro-well arrays for 3D shape control and high resolution analysis of single cells. Lab Chip 7, 1074–1077 (2007)
131. Park, J.Y., Lee, D.H., Lee, E.J., et al.: Study of cellular behaviors on concave and convex microstructures fabricated from elastic PDMS membranes. Lab Chip 9, 2043–2049 (2009)
132. Curtis, A., Wilkinson, C.: Topographical control of cells. Biomaterials 18, 1573–1583 (1997)
133. Kim, D.H., Lee, H.J., Lee, Y.K., et al.: Biomimetic nanopatterns as enabling tools for analysis and control of live cells. Adv. Mater. (2010, in press)
134. Kim, D.H., Han, K., Gupta, K., et al.: Mechanosensitivity of fibroblast cell shape and movement to anisotropic substratum topography gradients. Biomaterials 30, 5433–5444 (2009)
135. Charest, J.L., Eliason, M.T., Garcia, A.J., et al.: Combined microscale mechanical topography and chemical patterns on polymer cell culture substrates. Biomaterials 27, 2487–2494 (2006)
136. Motlagh, D., Hartman, T.J., Desai, T.A., et al.: Microfabricated grooves recapitulate neonatal myocyte connexin43 and N-cadherin expression and localization. J. Biomed. Mater. Res. A 67, 148–157 (2003)
137. Wang, L., Murthy, S.K., Fowle, W.H., et al.: Influence of micro-well biomimetic topography on intestinal epithelial Caco-2 cell phenotype. Biomaterials 30, 6825–6834 (2009)
138. Mai, J.Y., Sun, C., Li, S., et al.: A microfabricated platform probing cytoskeleton dynamics using multidirectional topographical cues. Biomed. Microdevices 9, 523–531 (2007)
139. Wong, J.Y., Leach, J.B., Brown, X.Q.: Balance of chemistry, topography, and mechanics at the cell-biomaterial interface: Issues and challenges for assessing the role of substrate mechanics on cell response. Surf. Sci. 570, 119–133 (2004)
140. Lim, J.Y., Donahue, H.J.: Cell sensing and response to micro-and nanostructured surfaces produced by chemical and topographic patterning. Tissue Eng. 13, 1879–1891 (2007)
141. Lam, M.T., Clem, W.C., Takayama, S.: Reversible on-demand cell alignment using reconfigurable microtopography. Biomaterials. 29, 1705–1712 (2008)
142. Dalby, M.J., Gadegaard, N., Tare, R., et al.: The control of human mesenchymal cell differentiation using nanoscale symmetry and disorder. Nat. Mater. 6, 997–1003 (2007)
143. Kim, D.H., Lipke, E.A., Kim, P., et al.: Nanoscale cues regulate the structure and function of macroscopic cardiac tissue constructs. Proc. Natl. Acad. Sci. USA 107, 565–570 (2010)
144. Brunetti, V., Maiorano, G., Rizzello, L., et al.: Neurons sense nanoscale roughness with nanometer sensitivity. Proc. Natl. Acad. Sci. USA 107, 6264–6269 (2010)
145. Young, E.W., Simmons, C.A.: Macro-and microscale fluid flow systems for endothelial cell biology. Lab Chip 10, 143–160 (2010)
146. van der Meer, A.D., Poot, A.A., Duits, M.H., et al.: Microfluidic technology in vascular research. J. Biomed. Biotechnol. 2009, 823148 (2009)
147. Brown, T.D.: Techniques for mechanical stimulation of cells in vitro: a review. J. Biomech. 33, 3–14 (2000)
148. Walker, G.M., Beebe, D.J.: A passive pumping method for microfluidic devices. Lab Chip 2, 131–134 (2002)
149. Meyvantsson, I., Warrick, J.W., Hayes, S., et al.: Automated cell culture in high density tubeless microfluidic device arrays. Lab Chip 8, 717–724 (2008)
150. Green, J.V., Kniazeva, T., Abedi, M., et al.: Effect of channel geometry on cell adhesion in microfluidic devices. Lab Chip 9, 677–685 (2009)
151. Usami, S., Chen, H.H., Zhao, Y.H., et al.: Design and construction of a linear shear-stress flow chamber. Ann. Biomed. Eng. 21, 77–83 (1993)
152. Melin, J., Quake, S.R.: Microfluidic large-scale integration: the evolution of design rules for biological automation. Annu. Rev. Biophys. Biomol. Struct. 36, 213–231 (2007)
153. Gomez-Sjoberg, R., Leyrat, A.A., Pirone, D.M., et al.: Versatile, fully automated, microfluidic cell culture system. Anal. Chem. 79, 8557–8563 (2007)
154. Gu, W., Zhu, X.Y., Futai, N., et al.: Computerized microfluidic cell culture using elastomeric channels and Braille displays. Proc. Natl. Acad. Sci. USA 101, 15861–15866 (2004)
155. Song, J.W., Gu, W., Futai, N., et al.: Computer-controlled microcirculatory support system for endothelial cell culture and shearing. Anal. Chem. 77, 3993–3999 (2005)
156. Tolan, N.V., Genes, L.I., Subasinghe, W., et al.: Personalized metabolic assessment of erythrocytes using microfluidic delivery to an array of luminescent wells. Anal. Chem. 81, 3102–3108 (2009)
157. Sim, W.Y., Park, S.W., Park, S.H. et al.: A pneumatic micro cell chip for the differentiation of human mesenchymal stem cells under mechanical stimulation. Lab Chip 7, 1775–1782 (2007)
158. Discher, D.E., Janmey, P., Wang, Y.L.: Tissue cells feel and respond to the stiffness of their substrate. Science 310, 1139–1143 (2005)
159. Pelham, R.J., Wang, Y.L.: Cell locomotion and focal adhesions are regulated by substrate flexibility. Proc. Natl. Acad. Sci. USA 94, 13661–13665 (1997)
160. Engler, A.J., Sen, S., Sweeney, H.L., et al.: Matrix elasticity directs stem cell lineage specification. Cell 126, 677–689 (2006)
161. Peyton, S.R., Raub, C.B., Keschrumrus, V.P., et al.: The use of poly(ethylene glycol) hydrogels to investigate the impact of ECM chemistry and mechanics on smooth muscle cells. Biomaterials 27, 4881–4893 (2006)
162. Khademhosseini, A., Yeh, J., Jon, S., et al.: Molded polyethylene glycol microstructures for capturing cells within microfluidic channels. Lab Chip 4, 425–430 (2004)
163. Moraes, C., Wang, G., Sun, Y., et al.: A microfabricated platform for high-throughput unconfined compression of micropatterned biomaterial arrays. Biomaterials 31, 577–584 (2010)
164. Liu, V.A., Bhatia, S.N.: Three-dimensional photopatterning of hydrogels containing living cells. Biomed.Microdevices 4, 257–266 (2002)
165. Liu J., Gao D., Li, H.F., et al.: Controlled photopolymerization of hydrogel microstructures inside microchannels for bioassays. Lab Chip 9, 1301–1305 (2009)
166. Jongpaiboonkit, L., King, W.J., Lyons, G.E., et al.: An adaptable hydrogel array format for 3-dimensional cell culture and analysis. Biomaterials 29, 3346–3356 (2008)
167. Jongpaiboonkit, L., King, W.J., Murphy, W.L.: Screening for 3D environments that support human mesenchymal stem cell viability using hydrogel arrays. Tissue Eng. Part A 15, 343– 353 (2009)
168. Zaari N., Rajagopalan, P., Kim, S.K. et al.: Photopolymerization in microfluidic gradient generators: microscale control of substrate compliance to manipulate cell response. Adv. Mater. 16, 2133–2137 (2004)
169. Gray, D.S., Tien, J., Chen, C.S.: Repositioning of cells by mechanotaxis on surfaces with micropatterned Young’s modulus. J. Biomed. Mater. Res.A. 66A, 605–614 (2003)
170. Du, Y., Hancock, M.J., He, J. et al.: Convection-driven generation of long-range material gradients. Biomaterials 31, 2686–2694 (2010)
171. Yip, C.Y., Chen, J.H., Zhao, R. et al.: Calcification by valve interstitial cells is regulated by the stiffness of the extracellular matrix. Arterioscler Thromb Vasc Biol. 29, 936–942 (2009).
172. Buxboim, A., Rajagopal, K., Brown, A.E.X., et al. How deeply cells feel: methods for thin gels. J. Phys. Condens. Matter. 22, 194116 (2010)
173. Bilodeau, K., Mantovani, D. Bioreactors for tissue engineering: focus on mechanical constraints. A comparative review. Tissue Eng. 12, 2367–2383 (2006)
174. Moraes, C., Chen, J.H., Sun, Y. et al. Microfabricated arrays for high-throughput screening of cellular response to cyclic substrate deformation. Lab Chip 10, 227–234 (2010)
175. Geddes-Klein, D.M., Schiffman, K.B., Meaney, D.F. Mechanisms and consequences of neuronal stretch injury in vitro differ with the model of trauma. J. Neurotrauma. 23 193–204 (2006)
176. Kamotani, Y., Bersano-Begey, T., Kato, N., et al. Individually programmable cell stretching microwell arrays actuated by a Braille display. Biomaterials 29, 2646–2655 (2008)
177. Kurpinski, K., Chu, J., Hashi, C., et al. Anisotropic mechanosensing by mesenchymal stem cells. Proc. Natl. Acad. Sci. USA 103, 16095–16100 (2006)
178. Wang, J.H., Yang, G., Li, Z.: Controlling cell responses to cyclic mechanical stretching. Ann. Biomed. Eng. 33, 337–342 (2005)
179. Tan, W., Scott, D., Belchenko, D., et al.: Development and evaluation of microdevices for studying anisotropic biaxial cyclic stretch on cells. Biomed.Microdevices 10, 869–882 (2008)
180. Gopalan, S.M., Flaim, C., Bhatia, S.N., et al.: Anisotropic stretch-induced hypertrophy in neonatal ventricular myocytes micropatterned on deformable elastomers. Biotechnol. Bioeng. 81, 578–587 (2003)
181. Bieler, F.H., Ott, C.E., Thompson, M.S., et al.: Biaxial cell stimulation: a mechanical validation. J. Biomech. 42, 1692–1696 (2009)
182. Sniadecki, N.J., Anguelouch, A., Yang, M.T. et al.: Magnetic microposts as an approach to apply forces to living cells. Proc. Natl. Acad. Sci. USA 104, 14553–14558 (2007)
183. Vartanian, K.B., Kirkpatrick, S.J., Hanson S.R., et al.: Endothelial cell cytoskeletal alignment independent of fluid shear stress on micropatterned surfaces. Biochem. Biophys. Res. Commun. 371, 787–792 (2008)
184. Toepke, M.W., Beebe, D.J.: PDMS absorption of small molecules and consequences in microfluidic applications. Lab Chip 6, 1484–1486 (2006)
185. Regehr, K.J., Domenech, M., Koepsel, J.T., et al.: Biological implications of polydimethylsiloxane-based microfluidic cell culture. Lab Chip 9, 2132–2139 (2009)
186. Moraes, C., Kagoma, Y.K., Beca, B.M., et al.: Integrating polyurethane culture substrates into poly(dimethylsiloxane) microdevices. Biomaterials 30, 5241–5250 (2009)