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Cellular and Molecular Bioengineering: A Tipping Point

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Abstract

In January of 2011, the Biomedical Engineering Society (BMES) and the Society for Physical Regulation in Biology and Medicine (SPRBM) held its inaugural Cellular and Molecular Bioengineering (CMBE) conference. The CMBE conference assembled worldwide leaders in the field of CMBE and held a very successful Round Table discussion among leaders. One of the action items was to collectively construct a white paper regarding the future of CMBE. Thus, the goal of this report is to emphasize the impact of CMBE as an emerging field, identify critical gaps in research that may be answered by the expertise of CMBE, and provide perspectives on enabling CMBE to address challenges in improving human health. Our goal is to provide constructive guidelines in shaping the future of CMBE.

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References

  1. Alberts, B. The Cell as a Collection of Protein Machines: preparing the Next Generation of Molecular Biologists. Cell 92:291, 1998.

    Article  Google Scholar 

  2. Baik, A. D., X. L. Lu, et al. Quasi-3D Cytoskeletal Dynamics of Osteocytes under Fluid Flow. Biophys. J. 99(9):2812–2820, 2010.

    Article  Google Scholar 

  3. Berdeaux, R. L., B. Diaz, L. Kim, and G. S. Martin. Active Rho is localized to podosomes induced by oncogenic Src and is required for their assembly and function. J. Cell Biol. 166:317–323, 2004.

    Article  Google Scholar 

  4. Bhaskar, H., and S. Singh. Live cell imaging: a computational perspective. J. Real-Time Image Proc. 1(3):195–212, 2007.

    Article  Google Scholar 

  5. Birukov, K. G. Cyclic stretch, reactive oxygen species, and vascular remodeling. Antioxid. Redox Signal. 11(7):1651–1667, 2009.

    Article  Google Scholar 

  6. Blencowe, M. Nanomechanical quantum limit. Science 304:56–57, 2004.

    Article  Google Scholar 

  7. Ceradini, D. J., A. R. Kulkarni, M. J. Callaghan, O. M. Tepper, N. Bastidas, M. E. Kleinman, J. M. Capla, R. D. Galiano, J. P. Levine, and G. C. Gurtner. Progenitor cell trafficking is regulated by hypoxic gradients through HIF-1 induction of SDF-1. Nat. Med. 10(8):858–864, 2004.

    Article  Google Scholar 

  8. Chang, E. I., R. G. Bonillas, S. El-ftesi, E. I. Chang, D. J. Ceradini, I. N. Vial, D. A. Chan, I. J. Michaels, 5th, and G. C. Gurtner. Tissue engineering using autologous microcirculatory beds as vascularized bioscaffolds. FASEB J. 23(3):906–915, 2009.

    Article  Google Scholar 

  9. Chang, M., E. Kistler, and G. W. Schmid-Schönbein. Disruption of the intestinal mucin layer during ischemia allows early entry of digestive enzymes into the intestinal wall. Shock 37(3):297–305, 2012.

    Article  Google Scholar 

  10. Chao, L. K., and R. M. Clegg. Foerster Resonance Energy Transfer (FRET) for Proteins. New York: Wiley Encyclopedia of Chemical Biology Advanced Review, 2008.

    Google Scholar 

  11. Chen, C. S., E. Ostuni, et al. Using self-assembled monolayers to pattern ECM proteins and cells on substrates. Methods Mol. Biol. 139:209–219, 2000.

    Google Scholar 

  12. Chien, S., A. Yoganathan, and V. C. Mow. Cellular and Molecular Bioengineering: celebration of the inauguration of a new international Journal of the Biomedical Engineering Society. Cell. Mol. Bioeng. 1:4–9, 2008.

    Article  Google Scholar 

  13. Clegg, R. M. Fluorescence resonance energy transfer. In: Fluorescence Imaging Spectroscopy and Microscopy, edited by X. F. Wang, and B. Herman. New York: Wiley, 1996, pp. 179–252.

    Google Scholar 

  14. Clegg, R. M. Nuts and bolts of excitation energy migration and energy transfer. In: Chlorophyll a Fluorescence: A Signature of Photosynthesis, edited by G. C. Papageorgiou, and Govindjee. Dordrecht: Springer, 2005, pp. 83–105.

    Google Scholar 

  15. Clegg, R. M., O. Holub, and C. Gohlke. Fluorescence lifetime-resolved imaging: measuring lifetimes in an image. Methods Enzymol. 360:509–542, 2003.

    Article  Google Scholar 

  16. Cole, N. B., et al. Diffusional mobility of Golgi proteins in membranes of living cells. Science 273:797–801, 1996.

    Article  Google Scholar 

  17. Cooke, J. P. Lymphangiogenesis: a potential new therapy for lymphedema? Circulation 125(7):853–855, 2012.

    Article  MathSciNet  Google Scholar 

  18. Dahl, K. N., et al. Mechanobiology and the microcirculation: cellular, nuclear and fluid mechanics. Microcirculation 17(3):179–191, 2010.

    Article  Google Scholar 

  19. Dayel, M. J., E. F. Hom, and A. S. Verkman. Diffusion of green fluorescent protein in the aqueous-phase lumen of endoplasmic reticulum. Biophys. J. 76:2843–2851, 1999.

    Article  Google Scholar 

  20. Dempsey, M. P., C. Hamou, I. J. Michaels, 5th, S. Ghali, L. Jazayeri, R. H. Grogan, and G. C. Gurtner. Using genetically modified microvascular free flaps to deliver local cancer immunotherapy with minimal systemic toxicity. Plast. Reconstr. Surg. 121:1541–1553, 2008.

    Article  Google Scholar 

  21. Discher, D., C. Dong, J. J. Fredberg, F. Guilak, D. Ingber, P. Janmey, R. D. Kamm, G. W. Schmid-Schönbein, and S. Weinbaum. Biomechanics: cell research and applications for the next decade. Ann. Biomed. Eng. 5:847–859, 2009.

    Article  Google Scholar 

  22. Dong, C. Adhesion and signaling of tumor cells to leukocytes and endothelium in cancer metastasis. Stud. Mechanobiol. Tissue Eng. Biomater. 4:477–521, 2011. doi:10.1007/8415_2010_21.

    Article  Google Scholar 

  23. Dvir, T., B. P. Timko, D. S. Kohane, and R. Langer. Nanotechnological strategies for engineering complex tissue. Nat. Nanotechnol. 6:13–22, 2011.

    Article  Google Scholar 

  24. Eichorst, J. P., H. Huang, R. M. Clegg, and Y. Wang. Phase differential enhancement to distinguish fluorescence components when monitoring molecular activity in live cells by FLIM. J. Fluoresc. 21(4):1763–1777, 2011.

    Article  Google Scholar 

  25. Elf, J., G. W. Li, and X. S. Xie. Probing transcription factor dynamics at the single-molecule level in a living cell. Science 316:1191–1194, 2007.

    Article  Google Scholar 

  26. Engler, A. J., S. Sen, et al. Matrix Elasticity Directs Stem Cell Lineage Specification. Cell 126(4):677–689, 2006.

    Article  Google Scholar 

  27. Eyckmans, J., et al. A hitchhiker’s guide to mechanobiology. Dev. Cell 21(1):35–47, 2001.

    Article  Google Scholar 

  28. Fichtlscherer, S., et al. Inflammatory markers and coronary artery disease. Curr. Opin. Pharmacol. 4(2):124–131, 2004.

    Article  Google Scholar 

  29. Fletcher, D. A., and R. D. Mullins. Cell mechanics and the cytoskeleton. Nature 463(7280):485–492, 2010.

    Article  Google Scholar 

  30. Franks, A. L., and J. E. Slansky. Multiple associations between a broad spectrum of autoimmune diseases, chronic inflammatory diseases and cancer. Anticancer Res. 32(4):1119–1136, 2012.

    Google Scholar 

  31. Freed, L. E., F. Guilak, et al. Advanced tools for tissue engineering: scaffolds, bioreactors, and signaling. Tissue Eng. 12(12):3285–3305, 2006.

    Article  Google Scholar 

  32. Ghali, S., K. A. Bhatt, M. P. Dempsey, D. M. Jones, S. Singh, S. Aarabi, P. E. Butler, R. L. Gallo, and G. C. Gurtner. Treating chronic wound infections with genetically modified free flaps. Plast. Reconstr. Surg. 123:1157–1168, 2009.

    Article  Google Scholar 

  33. Ghali, S., M. P. Dempsey, D. M. Jones, R. H. Grogan, P. E. Butler, and G. C. Gurtner. Plastic surgical delivery systems for targeted gene therapy. Ann. Plast. Surg. 60(3):323–332, 2008.

    Article  Google Scholar 

  34. Grashoff, C., B. D. Hoffman, M. D. Brenner, R. Zhou, M. Parsons, M. T. Yang, M. A. McLean, S. G. Sligar, C. S. Chen, T. Ha, and M. A. Schwartz. Measuring mechanical tension across vinculin reveals regulation of focal adhesion dynamics. Nature 466(7303):263–266, 2010.

    Article  Google Scholar 

  35. Grayson, W. L., M. Frohlick, et al. Engineering anatomically shaped human bone grafts. PNAS 107(8):3299–3304, 2010.

    Article  Google Scholar 

  36. Griffin, T. M., and F. Guilak. The Role of Mechanical Loading in the Onset of Osteoarthritis. Exerc. Sport Sci. Rev. 33(4):195–200, 2005.

    Article  Google Scholar 

  37. Grinnell, F. Fibroblast–collagen–matrix contraction: growth factor signalling and mechanical loading. Trends Cell Biol. 10(9):364–365, 2000.

    Article  Google Scholar 

  38. Guilak, F., D. M. Cohen, et al. Control of Stem Cell Fate by Physical Interactions with the Extracellular Matrix. Cell Stem Cell 5(1):17–26, 2009.

    Article  Google Scholar 

  39. Huo, B., X. L. Lu, C. T. Hung, K. D. Costa, Q. Xu, G. M. Whitesides, and X. E. Guo. Fluid Flow Induced Calcium Response in Bone Cell Network. Cell. Mol. Bioeng. 1(1):58–66, 2008.

    Article  Google Scholar 

  40. Jacobs, C. R., S. Temiyasathit, and A. B. Castillo. Osteocyte mechanobiology and pericellular mechanics. Annu. Rev. Biomed. Eng. 12:369–400, 2010.

    Article  Google Scholar 

  41. Janmey, P. A., and P. K. J. Kinnunen. Biophysical properties of lipids and dynamic membranes. Trends Cell Biol. 16(10):538–546, 2006.

    Article  Google Scholar 

  42. Janmey, P. A., and R. T. Miller. Mechanisms of mechanical signaling in development and disease. J. Cell Sci. 124:9–18, 2011.

    Article  Google Scholar 

  43. Khanna, P., E. Weidert, F. Vital-Lopez, A. Armaou, C. Maranas, and C. Dong. Model simulations reveal VCAM-1 augment PAK activation rates to amplify p38 MAPK and VE-cadherin phosphorylation. Cell. Mol. Bioeng. 4(4):656–669, 2011.

    Article  Google Scholar 

  44. Kumar, S., and V. M. Weaver. Mechanics, malignancy, and metastasis: the force journey of a tumor cell. Cancer Metastasis Rev. 28(1–2):113–127, 2009.

    Article  Google Scholar 

  45. Kunkel, M. T., Q. Ni, R. Y. Tsien, J. Zhang, and A. C. Newton. Spatio-temporal dynamics of protein kinase B/Akt signaling revealed by a genetically encoded fluorescent reporter. J. Biol. Chem. 280:5581–5587, 2005.

    Article  Google Scholar 

  46. LaHaye, M. D., O. Buu, B. Camarota, and K. C. Schwab. Approaching the quantum limit of a nanomechanical resonator. Science 304:74–77, 2004.

    Article  Google Scholar 

  47. Langer, R. S., and J. P. Vacanti. Tissue engineering: the challenges ahead. Sci. Am. 280(4):86–89, 1999.

    Article  Google Scholar 

  48. Lorizate, M., and H. G. Krausslich. Role of lipids in virus replication. Cold Spring Harb. Perspect. Biol. 3(10):a004820, 2011.

    Article  Google Scholar 

  49. Lukyanov, K. A., D. M. Chudakov, S. Lukyanov, and V. V. Verkhusha. Innovation: photoactivatable fluorescent proteins. Nat. Rev. Mol. Cell Biol. 6:885–891, 2005.

    Article  Google Scholar 

  50. Ma, Y. P., J. Wang, S. Liang, C. Dong, and Q. Du. Application of population dynamics to study heterotypic cell aggregations in the near-wall region of a shear flow. Cell. Mol. Bioeng. 3(1):3–19, 2010.

    Article  Google Scholar 

  51. MacKay, J. L., A. J. Keung, and S. Kumar. A genetic strategy for the dynamic and graded control of cell mechanics, motility, and matrix remodeling. Biophys. J. 102:434–442, 2012.

    Article  Google Scholar 

  52. Makino, A., E. R. Prossnitz, M. Bünemann, J. M. Wang, W. Yao, and G. W. Schmid-Schönbein. G Protein-coupled receptors serve as mechanosensors for fluid shear stress in neutrophils. Am. J. Physiol. Cell 290:C1633–C1639, 2006.

    Google Scholar 

  53. Mao, X., S. Lin, C. Dong, and T. J. Huang. Single-layer planar on-chip flow cytometer using microfluidic drifting based three-dimensional (3D) hydrodynamic focusing. Lab Chip 9:1583–1589, 2009.

    Article  Google Scholar 

  54. Meng, F., and F. Sachs. Visualizing dynamic cytoplasmic forces with a compliance-matched FRET sensor. J. Cell Sci. 124:261–269, 2011.

    Article  Google Scholar 

  55. Meng, F., and F. Sachs. Orientation-based FRET sensor for real-time imaging of cellular forces. J. Cell Sci. 125:743–750, 2012.

    Article  Google Scholar 

  56. Meng, F., T. Suchyna, E. Lasalovitch, R. M. Gronostajski, and F. Sachs. Real time FRET based detection of mechanical stress in cytoskeletal proteins. Cell. Mol. Bioeng. 4(2):148–159, 2011.

    Article  Google Scholar 

  57. Miyawaki, A., et al. Fluorescent indicators for Ca2+ based on green fluorescent proteins and calmodulin. Nature 388:882–887, 1997.

    Article  Google Scholar 

  58. Mochizuki, N., et al. Spatio-temporal images of growth-factor-induced activation of Ras and Rap1. Nature 411:1065–1068, 2001.

    Article  Google Scholar 

  59. Na, S., O. Collin, F. Chowdery, B. Tay, M. Ouyang, Y. Wang, and N. Wang. Rapid signal transduction in living cells is a unique feature of mechanotransduction. Proc. Natl. Acad. Sci. USA 105(18):6626–6631, 2008.

    Article  Google Scholar 

  60. Nehls, S., et al. Dynamics and retention of misfolded proteins in native ER membranes. Nat. Cell Biol. 2:288–295, 2000.

    Article  Google Scholar 

  61. Ott, H. C., B. Clippinger, C. Conrad, C. Schuetz, I. Pomerantseva, L. Ikonomou, D. Kotton, and J. P. Vacanti. Regeneration and orthotopic transplantation of a bioartificial lung. Nat. Med. 16(8):927–933, 2010.

    Article  Google Scholar 

  62. Ott, H. C., T. S. Matthiesen, S. K. Goh, L. D. Black, S. M. Kren, T. I. Netoff, and D. A. Taylor. Perfusion-decellularized matrix: using nature’s platform to engineer a bioartificial heart. Nat. Med. 14(2):213–221, 2008.

    Article  Google Scholar 

  63. Ouyang, M., J. Sun, S. Chien, and Y. Wang. Determination of hierarchical relationship of Src and Rac at subcellular locations with FRET biosensors. Proc. Natl Acad. Sci. USA 105:14353–14358, 2008.

    Article  Google Scholar 

  64. Ouyang, M., et al. Simultaneous visualization of protumorigenic Src and MT1-MMP activities with fluorescence resonance energy transfer. Cancer Res. 70:2204–2212, 2010.

    Article  Google Scholar 

  65. Palestini, P., et al. Compositional changes in lipid microdomains of air–blood barrier plasma membranes in pulmonary interstitial edema. J. Appl. Physiol. 95:1446–1452, 2003.

    Google Scholar 

  66. Park, T.-H., N. Mirin, J. B. Lassiter, C. L. Nehl, N. J. Halas, and P. Nordlander. Optical properties of a nanosized hole in a thin metallic film. ACS Nano 2:25–32, 2004.

    Article  Google Scholar 

  67. Pertz, O., L. Hodgson, R. L. Klemke, and K. M. Hahn. Spatiotemporal dynamics of RhoA activity in migrating cells. Nature 440:1069–1072, 2006.

    Article  Google Scholar 

  68. Phair, R. D., and T. Misteli. Kinetic modelling approaches to in vivo imaging. Nat. Rev. Mol. Cell Biol. 2:898–907, 2001.

    Article  Google Scholar 

  69. Pinot, F., et al. Curosurf modulates cAMP accumulation in human monocytes through a membrane-controlled mechanism Am. J. Physiol. Lung Cell. Mol. Physiol. 278:L99–L104, 2000.

    Google Scholar 

  70. Poh, Y. C., S. P. Shevtsov, F. Chowdhury, D. C. Wu, S. Na, M. Dundr, and N. Wang. Dynamic force-induced direct dissociation of protein complexes in a nuclear body in living cells. Nat. Commun. 3:866, 2012. doi:10.1038/ncomms1873.

    Google Scholar 

  71. Reits, E. A., and J. J. Neefjes. From fixed to FRAP: measuring protein mobility and activity in living cells. Nat. Cell Biol. 3:E145–E147, 2001.

    Article  Google Scholar 

  72. Round Table. Future of Cellular and Molecular Bioengineering and SPRBM. Cell Mol. Bioeng. 4(2):265–269, 2011.

    Article  Google Scholar 

  73. Schmid-Schonbein, G. W. Biomechanical aspects of the auto-digestion theory. Mol. Cell Biomech. 5(2):83–95, 2008.

    Google Scholar 

  74. Schneider, P. C., and R. M. Clegg. Rapid acquisition, analysis, and display of fluorescence lifetime-resolved images for real-time applications. Rev. Sci. Instrum. 68:4107–4119, 1997.

    Article  Google Scholar 

  75. Sirbuly, D. J., A. Tao, M. Law, R. Fan, and P. Yang. Multifunctional nanowire evanescent wave optical sensors. Adv. Mater. 19:61–66, 2007.

    Article  Google Scholar 

  76. Skerry, T. M. The response of bone to mechanical loading and disuse: fundamental principles and influences on osteoblast/osteocyte homeostasis. Arch. Biochem. Biophys. 473(2):117–123, 2008.

    Article  Google Scholar 

  77. Susarla, S. M., E. Swanson, and C. R. Gordon. Craniomaxillofacial reconstruction using allotransplantation and tissue engineering: challenges, opportunities, and potential synergy. Ann. Plast. Surg. 67(6):655–661, 2011.

    Article  Google Scholar 

  78. Thomas, S. M., and J. S. Brugge. Cellular functions regulated by Src family kinases. Annu. Rev. Cell Dev. Biol. 13:513–609, 1997.

    Article  Google Scholar 

  79. Ting, A. Y., K. H. Kain, R. L. Klemke, and R. Y. Tsien. Genetically encoded fluorescent reporters of protein tyrosine kinase activities in living cells. Proc. Natl Acad. Sci. USA 98:15003–15008, 2001.

    Article  Google Scholar 

  80. Torchilin, V. P. Recent advances with liposomes as pharmaceutical carriers. Nat. Rev. Drug Discovery 4:145–160, 2005.

    Article  Google Scholar 

  81. Tsien, R. Y. The green fluorescent protein. Annu. Rev. Biochem. 67:509–544, 1998.

    Article  Google Scholar 

  82. Vacanti, J. P., and R. Langer. Tissue engineering: the design and fabrication of living replacement devices for surgical reconstruction and transplantation. Lancet 354 (Suppl 1):SI32–SI34, 1999.

    Google Scholar 

  83. Vanepps, J. S., and D. A. Vorp. Mechano-pathobiology of atherogenesis: a review. J. Surg. Res. 142(1):202–217, 2007.

    Article  Google Scholar 

  84. Violin, J. D., J. Zhang, R. Y. Tsien, and A. C. Newton. A genetically encoded fluorescent reporter reveals oscillatory phosphorylation by protein kinase C. J. Cell Biol. 161:899–909, 2003.

    Article  Google Scholar 

  85. Wallrabe, H., and A. Periasamy. Imaging protein molecules using FRET and FLIM microscopy. Curr. Opin. Biotechnol. 16:19–27, 2005.

    Article  Google Scholar 

  86. Wang, Y., E. L. Botvinick, Y. Zhao, M. W. Berns, S. Usami, R. Y. Tsien, and S. Chien. Visualizing the mechanical activation of Src. Nature 434(7036):1040–1045, 2005.

    Article  Google Scholar 

  87. Wang, Y., J. Y. Shyy, and S. Chien. Fluorescence proteins, live-cell imaging, and mechanobiology: seeing is believing. Annu. Rev. Biomed. Eng. 10:1–38, 2008.

    Article  MATH  Google Scholar 

  88. Wang, Y., et al. Visualizing the mechanical activation of Src. Nature 434:1040–1045, 2005.

    Article  Google Scholar 

  89. Wozniak, M. A., and C. S. Chen. Mechanotransduction in development: a growing role for contractility. Nat. Rev. Mol. Cell Biol. 10:34–43, 2009.

    Article  Google Scholar 

  90. Yu, J., J. Xiao, X. Ren, K. Lao, and X. S. Xie. Probing gene expression in live cells, one protein molecule at a time. Science 311:1600–1603, 2006.

    Article  Google Scholar 

  91. Zhang, J., C. J. Hupfeld, S. S. Taylor, J. M. Olefsky, and R. Y. Tsien. Insulin disrupts beta-adrenergic signalling to protein kinase A in adipocytes. Nature 437:569–573, 2005.

    Article  Google Scholar 

  92. Zhang, J., Y. Ma, S. S. Taylor, and R. Y. Tsien. Genetically encoded reporters of protein kinase A activity reveal impact of substrate tethering. Proc. Natl Acad. Sci. USA 98:14997–15002, 2001.

    Article  Google Scholar 

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Acknowledgments

We would like to acknowledge following individuals who have contributed in various forms to this paper (in alphabetical order): Alissa Morss Clyne, Dennis E. Discher, Daniel A. Fletcher, William H. Guilford, Jay D. Humphrey, Clark T. Hung, Nic D. Leipzig, Elizabeth G. Loboa, Daniel J. Müller, David J. Odde, Yixian Qin, Masaaki Sato, Michael S. Sacks, Robert T. Tranquillo, James H.-C. Wang, Sihong Wang. We would also like to thank Ms. Genya Gurvich for her assistance in manuscript preparation. XEG acknowledges partial funding support from NIH (R13EB012902, R01AR052461, and R21AR059917).

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Brown, G., Butler, P.J., Chang, D.W. et al. Cellular and Molecular Bioengineering: A Tipping Point. Cel. Mol. Bioeng. 5, 239–253 (2012). https://doi.org/10.1007/s12195-012-0246-7

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