Tribology Letters

, 66:141 | Cite as

Considerations for Biotribometers: Cells, Gels, and Tissues

  • Juan Manuel Urueña
  • Samuel M. Hart
  • Derek L. Hood
  • Eric O. McGhee
  • Sean R. Niemi
  • Kyle D. Schulze
  • Padraic P. Levings
  • W. Gregory Sawyer
  • Angela A. Pitenis


Tribological evaluation of biological materials, such as cells and tissues, present both opportunities and challenges to experimentalists. When working with living materials, maintaining homeostasis during testing in vitro or in vivo often requires appropriate control of the environment, selection of the testing time and duration, applied loads, and shear stresses. This manuscript provides much of the background and design information used in the development of a microtribometer that has been modified to perform biotribology measurements in vitro. The focus of this manuscript is on mammalian cells in monolayer, and a series of order-of-magnitude calculations are used to inform future instrument designs and considerations, including: sliding speed ranges from 10 nm/s to 100 mm/s, contact pressures less than 6 kPa, temperature ~ 37 °C, and contact areas on the order of 1,000’s of µm2. The design and development of these biotribology instruments enable in situ fluorescence microscopy and allow for statistically significant gene expression analyses such as quantitative reverse-transcription polymerase chain-reaction (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA).


Biotribometer Biomedicine Biocompatibility In Situ Tribology 



This work was supported by Alcon Laboratories.


  1. 1.
    Reeve, L., Baldrick, P.: Biocompatibility assessments for medical devices – evolving regulatory considerations. Exp. Rev. Med. Devices. 14, 161–167 (2017). CrossRefGoogle Scholar
  2. 2.
    Center for Devices and Radiological Health U.S. Food and Drug Administration. Anaplastic Large Cell Lymphoma (ALCL) In Women with Breast Implants: Preliminary FDA Findings and Analyses, Accessed Nov 9 2017
  3. 3.
    U.S. Food and Drug Administration. Medical Device Reports of Breast Implant-Associated Anaplastic Large Cell Lymphoma, Accessed April 15 2018
  4. 4.
    Nichols, J.J., Willcox, M.D.P., Bron, A.J., Belmonte, C., Ciolino, J.B., Craig, J.P., Dogru, M., Foulks, G.N., Jones, L., Nelson, J.D., Nichols, K.K., Purslow, C., Schaumberg, D.A., Stapleton, F., Sullivan, D.A.: The TFOS international workshop on contact lens discomfort: executive summary. Investig. Ophthalmol. Vis. Sci. 54, 7–13: (2013). CrossRefGoogle Scholar
  5. 5.
    Efron, N.: Contact lens wear is intrinsically inflammatory. Clin. Exp. Optom. 100, 3–19 (2017). CrossRefGoogle Scholar
  6. 6.
    Efron, N.: Rethinking contact lens discomfort. Clin. Exp. Optom. 101, 1–3 (2018). CrossRefGoogle Scholar
  7. 7.
    Qin, G., Baidouri, H., Glasser, A., Raghunathan, V., Morris, C., Maltseva, I., McDermott, A.M.: Development of an in vitro model to study the biological effects of blinking. Ocul. Surf. (2018). CrossRefGoogle Scholar
  8. 8.
    Pitenis, A.A., Urueña, J.M., Hart, S.M., O’Bryan, C.S., Marshall, S.L., Levings, P.P., Angelini, T.E., Sawyer, W.G.: Friction-induced inflammation. Tribol. Lett. 66, 81 (2018). CrossRefGoogle Scholar
  9. 9.
    Cobb, J.A., Dunn, A.C., Kwon, J., Sarntinoranont, M., Sawyer, W.G., Tran-Son-Tay, R.: A novel method for low load friction testing on living cells. Biotechnol. Lett. 30, 801–806 (2008). CrossRefGoogle Scholar
  10. 10.
    Dunn, A.C., Zaveri, T.D., Keselowsky, B.G., Sawyer, W.G.: Macroscopic friction coefficient measurements on living endothelial cells. Tribol. Lett. 27, 233–238 (2007). CrossRefGoogle Scholar
  11. 11.
    Dunn, A.C., Cobb, J.A., Kantzios, A.N., Lee, S.J., Sarntinoranont, M., Tran-Son-Tay, R., Sawyer, W.G.: Friction coefficient measurement of hydrogel materials on living epithelial cells. Tribol. Lett. 30, 13–19 (2008). CrossRefGoogle Scholar
  12. 12.
    Straehla, J.P., Limpoco, F.T., Dolgova, N.V., Keselowsky, B.G., Sawyer, W.G., Perry, S.S.: Nanomechanical probes of single corneal epithelial cells: Shear stress and elastic modulus. Tribol. Lett. 38, 107–113 (2010). CrossRefGoogle Scholar
  13. 13.
    Sterner, O., Aeschlimann, R., Zürcher, S., Scales, C., Riederer, D., Spencer, N.D., Tosatti, S.G.P.: Tribological classification of contact lenses: from coefficient of friction to sliding work. Tribol. Lett. 63, 9 (2016). CrossRefGoogle Scholar
  14. 14.
    Pitenis, A.A., Urueña, J.M., Hormel, T.T., Bhattacharjee, T., Niemi, S.R., Marshall, S.L., Hart, S.M., Schulze, K.D., Angelini, T.E., Sawyer, W.G.G.: Corneal cell friction: survival, lubricity, tear films, and mucin production over extended duration in vitro studies. Biotribology. 11, 77–83 (2017). CrossRefGoogle Scholar
  15. 15.
    Pitenis, A.A., Urueña, J.M., McGhee, E.O., Hart, S.M., Reale, E.R., Kim, J., Schulze, K.D., Marshall, S.L., Bennett, A.I., Niemi, S.R., Angelini, T.E., Sawyer, W.G., Dunn, A.C.: Challenges and opportunities in soft tribology. Tribol. Mater. Surfaces Interfaces. 11, 180–186 (2017). CrossRefGoogle Scholar
  16. 16.
    Zehnder, S.M., Wiatt, M.K., Uruena, J.M., Dunn, A.C., Sawyer, W.G., Angelini, T.E.: Multicellular density fluctuations in epithelial monolayers. Phys. Rev. E. 92, 032729 (2015). CrossRefGoogle Scholar
  17. 17.
    Schulze, K.D., Zehnder, S.M., Urueña, J.M., Bhattacharjee, T., Sawyer, W.G., Angelini, T.E.: Elastic modulus and hydraulic permeability of MDCK monolayers. J. Biomech. 53, 210–213 (2017). CrossRefGoogle Scholar
  18. 18.
    Rennie, A.C., Dickrell, P.L., Sawyer, W.G.: Friction coefficient of soft contact lenses: measurements and modeling. Tribol. Lett. 18, 499–504 (2005). CrossRefGoogle Scholar
  19. 19.
    Krick, B.A., Vail, J.R., Persson, B.N.J., Sawyer, W.G.: Optical in situ micro tribometer for analysis of real contact area for contact mechanics, adhesion, and sliding experiments. Tribol. Lett. 45, 185–194 (2012). CrossRefGoogle Scholar
  20. 20.
    Urueña, J.M., Pitenis, A.A., Harris, K.L., Sawyer, W.G.: Evolution and wear of fluoropolymer transfer films. Tribol. Lett. 57, 9 (2015). CrossRefGoogle Scholar
  21. 21.
    Pitenis, A.A., Urueña, J.M., Schulze, K.D., Nixon, R.M., Dunn, A.C., Krick, B.A., Sawyer, W.G., Angelini, T.E., Sawyer, G., Angelini, T.E.: Polymer fluctuation lubrication in hydrogel gemini interfaces. Soft Matter. 10, 8955–8962 (2014). CrossRefGoogle Scholar
  22. 22.
    Urueña, J.M., Pitenis, A.A., Nixon, R.M., Schulze, K.D., Angelini, T.E., Sawyer, W.G.: Mesh Size control of polymer fluctuation lubrication in gemini hydrogels. Biotribology. 1–2, 24–29 (2015). CrossRefGoogle Scholar
  23. 23.
    Pitenis, A.A., Manuel Urueña, J., Cooper, A.C., Angelini, T.E., Sawyer, W.G.: Superlubricity in gemini hydrogels. J. Tribol. 138, 042103 (2016). CrossRefGoogle Scholar
  24. 24.
    Schmitz, T.L., Action, J.E., Ziegert, J.C., Sawyer, W.G.: The difficulty of measuring low friction: Uncertainty analysis for friction coefficient measurements. J. Tribol. 127, 673 (2005). CrossRefGoogle Scholar
  25. 25.
    Burris, D.L., Sawyer, W.G.: Addressing practical challenges of low friction coefficient measurements. Tribol. Lett. 35, 17–23 (2009). CrossRefGoogle Scholar
  26. 26.
    Schulze, K.D., Hart, S.M., Marshall, S.L., O’Bryan, C.S., Urueña, J.M., Pitenis, A.A., Sawyer, W.G., Angelini, T.E.: Polymer osmotic pressure in hydrogel contact mechanics. Biotribology. 11, 3–7 (2017). CrossRefGoogle Scholar
  27. 27.
    Urueña, J.M., McGhee, E.O., Angelini, T.E., Dowson, D., Sawyer, W.G., Pitenis, A.A.: Normal load scaling of friction in gemini hydrogels. Biotribology. 13, 30–35 (2018). CrossRefGoogle Scholar
  28. 28.
    Johnson, K.L.: Contact Mechanics. Cambridge University Press, Cambridge (1985)CrossRefGoogle Scholar
  29. 29.
    Garcia, M., Schulze, K.D., O’Bryan, C.S., Bhattacharjee, T., Sawyer, W.G., Angelini, T.E.: Eliminating the surface location from soft matter contact mechanics measurements. Tribol. Mater. Surfaces Interfaces. 11, 187–192 (2017). CrossRefGoogle Scholar
  30. 30.
    Marshall, S.L., Schulze, K.D., Hart, S.M., Urueña, J.M., McGhee, E.O., Bennett, A.I., Pitenis, A.A., O’Bryan, C.S., Angelini, T.E., Sawyer, W.G.: Spherically capped membrane probes for low contact pressure tribology. Biotribology. 11, 69–72 (2017). CrossRefGoogle Scholar
  31. 31.
    Bhattacharjee, T., Zehnder, S.M., Rowe, K.G., Jain, S., Nixon, R.M., Sawyer, W.G., Angelini, T.E.: Writing in the granular gel medium. Sci. Adv. 1, e1500655–e1500655 (2015). CrossRefGoogle Scholar
  32. 32.
    Bhattacharjee, T., Gil, C.J., Marshall, S.L., Urueña, J.M., O’Bryan, C.S., Carstens, M., Keselowsky, B., Palmer, G.D., Ghivizzani, S., Gibbs, C.P., Sawyer, W.G., Angelini, T.E.: Liquid-like solids support Cells in 3D. ACS biomater. Sci. Eng. 2, 1787–1795 (2016). CrossRefGoogle Scholar
  33. 33.
    O’Bryan, C.S., Bhattacharjee, T., Hart, S., Kabb, C.P., Schulze, K.D., Chilakala, I., Sumerlin, B.S., Sawyer, W.G., Angelini, T.E.: Self-assembled micro-organogels for 3D printing silicone structures. Sci. Adv. 3, e1602800 (2017). CrossRefGoogle Scholar
  34. 34.
    O’Bryan, C.S., Bhattacharjee, T., Niemi, S.R., Balachandar, S., Baldwin, N., Ellison, S.T., Taylor, C.R., Sawyer, W.G., Angelini, T.E.: Three-dimensional printing with sacrificial materials for soft matter manufacturing. MRS Bull. 42, 571–577 (2017). CrossRefGoogle Scholar
  35. 35.
    Svoboda, K., Block, S.M.: Force and velocity measured for single kinesin molecules. Cell. 77, 773–784 (1994). CrossRefGoogle Scholar
  36. 36.
    Dunn, A.C., Tichy, J.A., Uruenã, J.M., Sawyer, W.G.G., Urueña, J.M., Sawyer, W.G.G.: Lubrication regimes in contact lens wear during a blink. Tribol. Int. 63, 45–50 (2013). CrossRefGoogle Scholar
  37. 37.
    Dowson, D.: Paper 12: Modes of Lubrication in Human Joints. Proc. Inst. Mech. Eng. Conf. Proc. 181, 45–54: (1966). CrossRefGoogle Scholar
  38. 38.
    Hamrock, B.J., Dowson, D.: Elastohydrodynamic Lubrication of elliptical contacts for materials of low elastic modulus I—fully flooded conjunction. J. Lubr. Technol. 100, 236 (1978). CrossRefGoogle Scholar
  39. 39.
    Kapitza, P.L.: Hydrodynamic theory of lubrication during rolling. Zh. Tekh. Fiz. 25, 747–762 (1955)Google Scholar
  40. 40.
    Dunn, A.C., Urueña, J.M., Huo, Y., Perry, S.S., Angelini, T.E., Sawyer, W.G.: Lubricity of surface hydrogel layers. Tribol. Lett. 49, 371–378 (2013). CrossRefGoogle Scholar
  41. 41.
    Schulze, K.D., Bennett, A.I., Marshall, S., Rowe, K.G., Dunn, A.C.: Real area of contact in a soft transparent interface by particle exclusion microscopy. J. Tribol. 138, 041404 (2016). CrossRefGoogle Scholar
  42. 42.
    McGhee, E.O., Pitenis, A.A., Urueña, J.M., Schulze, K.D., McGhee, A.J., O’Bryan, C.S., Bhattacharjee, T., Angelini, T.E., Sawyer, W.G.: In situ measurements of contact dynamics in speed-dependent hydrogel friction. Biotribology. 13, 23–29 (2018). CrossRefGoogle Scholar
  43. 43.
    Lichtman, J.W., Conchello, J.-A.: Fluorescence microscopy. Nat. Methods. 2, 910–919 (2005). CrossRefGoogle Scholar
  44. 44.
    Shaner, N.C., Steinbach, P.A., Tsien, R.Y.: A guide to choosing fluorescent proteins. Nat. Methods. 2, 905–909 (2005). CrossRefGoogle Scholar
  45. 45.
    Berridge, M.J., Bootman, M.D., Roderick, H.L.: Calcium signalling: dynamics, homeostasis and remodelling. Nat. Rev. Mol. Cell Biol. 4, 517–529 (2003). CrossRefGoogle Scholar
  46. 46.
    de Oliveira, C.M.B., Sakata, R.K., Issy, A.M., Gerola, L.R., Salomão, R.: Cytokines and Pain. Rev. Bras. Anestesiol. 61, 255–265 (2011). CrossRefGoogle Scholar
  47. 47.
    Zhang, J.-M., An, J.: Cytokines, inflammation, and pain. Int. Anesthesiol. Clin. 45, 27–37 (2007). CrossRefGoogle Scholar
  48. 48.
    Milo, R., Phillips, R.: Cell biology by the numbers. Garland Science, Taylor & Francis Group, New York (2016)Google Scholar
  49. 49.
    Ramsköld, D., Luo, S., Wang, Y.-C., Li, R., Deng, Q., Faridani, O.R., Daniels, G.A., Khrebtukova, I., Loring, J.F., Laurent, L.C., Schroth, G.P., Sandberg, R.: Full-length mRNA-Seq from single-cell levels of RNA and individual circulating tumor cells. Nat. Biotechnol. 30, 777–782 (2012). CrossRefGoogle Scholar
  50. 50.
    Shapiro, E., Biezuner, T., Linnarsson, S.: Single-cell sequencing-based technologies will revolutionize whole-organism science. Nat. Rev. Genet. 14, 618–630 (2013). CrossRefGoogle Scholar
  51. 51.
    Milo, R.: What is the total number of protein molecules per cell volume? A call to rethink some published values. BioEssays. 35, 1050–1055 (2013). CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Juan Manuel Urueña
    • 1
  • Samuel M. Hart
    • 1
  • Derek L. Hood
    • 1
  • Eric O. McGhee
    • 1
  • Sean R. Niemi
    • 1
  • Kyle D. Schulze
    • 1
  • Padraic P. Levings
    • 2
  • W. Gregory Sawyer
    • 1
    • 3
    • 4
  • Angela A. Pitenis
    • 1
  1. 1.Department of Mechanical and Aerospace EngineeringUniversity of FloridaGainesvilleUSA
  2. 2.Department of Orthopaedics and RehabilitationUniversity of FloridaGainesvilleUSA
  3. 3.Department of Materials Science and EngineeringUniversity of FloridaGainesvilleUSA
  4. 4.Department of Biomedical EngineeringUniversity of FloridaGainesvilleUSA

Personalised recommendations