Abstract
Today the combination of several microscopy techniques over a sample can be performed at the same time on the same region. To fully capitalize on their complementarities and reveal new properties or behaviors as well as to present them in a new and attractive way, enhancing the experimental data exploration is a key issue. Especially, science education at micro and nanoscale is often limited by the complexity of making complicated knowledge accessible and easily remembered by the larger public. We propose an “out of the box” way to introduce complex scientific subjects like cell biology and polymer micro-rheology using haptic display and virtual reality. To reach this ambitious goal, firstly we combined the advantages of the Atomic Force Microscopy (AFM) and Fluorescence Microscopy (FM) in order to get complementary real experimental data on fixed and living isolated animal cells adhering on a protein micro-pattern or on a collagen-coated soft hydrogel. Secondly, thanks to the recent and fast AFM modes (PeakForce and Quantitative Imaging) dedicated to nanomechanical investigations, we achieved high resolution mapping images of the cell morphology, architecture and local mechanical properties. Then this set of data was implemented in a free simulation engine connected to a low-cost haptic device to create a virtual and interactive cell or polymer environment. In this environment, the user can explore the stiffness across three soft samples and can relate it to specific sample components. This dedicated visuo-haptic environment provides a novel sensory approach of the cell biology and/or micro(bio)mechanics through an active exploration of a set of scientific experimental data. This work paves the way to an affordable interactive and multisensory VR platform where various AFM images recorded in Peak Force or Quantitative Imaging, could be load in order to be actively explored; this approach fits into the emerging field of touching data.
Similar content being viewed by others
References
Jansen K, Atherton P, Ballestrem C (2017) Mechanotransduction at the cell-matrix interface. Semin Cell Dev Biol 71:75–83
Park JS, Chu JS, Tsou AD, Diop R, Tang Z, Wang A, Li S (2011) The effect of matrix stiffness on the differentiation of mesenchymal stem cells in response to TGF-β. Biomaterials 32(16):3921–3930
Eroshenko N, Ramachandran R, Yadavalli VK, Rao RR (2013) Effect of substrate stiffness on early human embryonic stem cell differentiation. J Biol Eng 7:7
Rauzi M, Verant P, Lecuit T, Lenne P-F (2008) Nature and anisotropy of cortical forces orienting drosophila tissue morphogenesis. Nat Cell Biol 10:1401–1410
Lekka M (2016) Discrimination between normal and cancerous cells using AFM. BioNanoScience 6:65–80
Zhu X, Zhang N, Wang Z, Liu X (2016) Investigation of work of adhesion of biological cell (human hepatocellular carcinoma) by AFM nanoindentation. J Micro-Bio-Robot 11:47–55
Wang N (2017) Review of cellular mechanotransduction. J Phys D Appl Phys 50:233002
Bivall P, Ainsworth S, Tibell LAE (2011) Do haptic representations help complex molecular learning? Sci Educ 95:700–719
Millet G, Lécuyer A, Burkhardt J-M, Haliyo S, Régnier S (2013) Haptics and graphic analogies for the understanding of atomic force microscopy. International Journal of Human-Computer Studies 71:608–626
Basdogan C, Sedef M, Harders M, Wesarg S (2007) Vr-based simulators for training in minimally invasive surgery. IEEE Comput Graph Appl 27:54–66
Minogue J, Gail Jones M, Broadwell B, Oppewall T (2006) The impact of haptic augmentation on middle school students’ conceptions of the animal cell. Virtual Reality 10:293–305
Ladjal H, Hanus J, Pillarisetti A, Keefer C, Ferreira A, Desai JP (2010) Realistic visual and haptic feedback simulator for real-time cell indentation, in 2010 IEEE/RSJ International Conference on Intelligent Robots and Systems, pp. 3993–3998
Marliere S, Marchi F, Florens JL, Luciani A, Chevrier J (2008) An augmented reality nanomanipulator for learning nanophysics: The “nanolearner” platform, in 2008 International Conference on Cyberworlds,) pp. 94–101
Butt H-J, Cappella B, Kappl M (2005) Force measurements with the atomic force microscope: technique, interpretation and applications. Surf Sci Rep 59(1):1–152
Radotic K, Roduit C, Simonovic J, Hornitschek P, Fankhauser C, Mutavdžic D, Steinbach G, Dietler G, Kasas S (2012) Atomic force microscopy stiffness tomography on living Arabidopsis thaliana cells reveals the mechanical properties of surface and deep cell-wall layers during growth. Biophys J 103:386–394
Lu L, Oswald SJ, Ngu H, Yin FC-P (2008) Mechanical properties of actin stress fibers in living cells. Biophysical journal 95(12):6060–6071
Calzado-Martín A, Encinar M, Tamayo J, Calleja M, San Paulo A (2016) Effect of actin organization on the stiffness of living breast cancer cells revealed by peak-force modulation atomic force microscopy. ACS Nano 10(3):3365–3374
JPK Instruments AG, « Application note: QITM mode - Quantitative imaging with the NanoWizard 3 AFM »
Schillers H, Medalsy I, Hu S, Slade AL, Shaw JE (2016) Peakforce tapping resolves individual microvilli on living cells. J Mol Recognit 29:95–101
Cartagna-Ruvera AX, Wang WH, Geahlen RL, Raman A (2015) Fast multi-frequency and quantitative nanomechanical mapping of live cell using the atomic force microscope. Sci Rep 5:p11692
Alsteens D, Trabelsi H, Soumillion P, et Dufrêne YF (2013) Multiparametric atomic force microscopy imaging of single bacteriophages extruding from living bacteria. Nature Communications, vol. 4
Babu PKV, Rianna C, Mirastschijski U, Radmacher M (2019) Nano-mechanical mapping of interdependent cell and ECM mechanics by AFM force spectroscopy. Sci Rep 9:1–19
C. Petit, M. Kechiche, I. A. Ivan, R. Toscano, V. Bolcato, E. Planus, and F. Marchi, « Characterization of micro/nano-rheology properties of soft and biological matter combined with a virtual haptic exploration » , International conference on Manipulation, Automation and Robotics at Small Scales (MARSS) IEEE Helsinki, Finland, pp. 1–6 (2019)
Kechiche M, Petit C, Marchi F, Toscano R, Bolcato V, Planus E, Ivan IA (2019) Haptic exploration of a cell morphology and rheology properties at nanoscale using AFM Peak-Force mode. IEEE World Haptics Conference, Tokyo, Japan, July 9–12
CYTOO, « CYTOOchips™ Starter’s A x18 »: https://cytoo.com/system/files_force/node/chips/files/CytooChips-Standard_1.pdf?download=1
Ahmed WW, Fodor É, Betz T (2015) Active cell mechanics: measurement and theory. Biochimica et Biophysica Acta (BBA) Molecular Cell Research 1853(11, Part B):3083–3094
Livne A, Geiger B (2016) The inner workings of stress fibers − from contractile machinery to focal adhesions and back. J Cell Sci 129:1293–1304
Théry M (2010) Micropatterning as a tool to decipher cell morphogenesis and functions. J Cell Sci 123:4201–4213
Rigato A, Rico F, Eghiaian F, Piel M, Scheuring S (2015) Atomic force microscopy mechanical mapping of micropatterned cells shows adhesion geometry-dependent mechanical response on local and global scales. ACS Nano 9:5846–5856
Petit C, Guignandon A, Avril S (2019) Traction force measurements of human aortic smooth muscle cells reveal a motor-clutch behavior. Molecular and Cell Biomechanics 16:87–108
Goffin JM, Pittet P, Csucs G, Lussi JW, Meister J-J, Hinz B (2006) Focal adhesion size controls tension-dependent recruitment of α-smooth muscle actin to stress fibers. J Cell Biol 172:259–268
Chen J, Li H, SundarRaj N, Wang JH-C (2007) Alpha-smooth muscle actin expression enhances cell traction force. Cell Motil Cytoskeleton 64:248–257
Binnig G, Quate CF, Gerber C (1986) Atomic force microscope. Phys Rev Lett 56:930–933
Meyer E, Hug HJ, Bennewitz R (2004) Introduction to scanning probe microscopy. Springer Berlin Heidelberg, Berlin, Heidelberg
Lévy R, Maaloum M (2001) Measuring the spring constant of atomic force microscope cantilevers: thermal fluctuations and other methods. Nanotechnology 13:33–37
Hansma PK, Cleveland JP, Radmacher M, Walters DA, Hillner PE, Bezanilla M, Fritz M, Vie D, Hansma HG, Prater CB, Massie J, Fukunaga L, Gurley J, Elings V (1994) Tapping mode atomic force microscopy in liquids. Appl Phys Lett 64:1738–1740
Morkvėnaitė-Vilkončienė I, Ramanavičienė A, Ramanavičius A (2013) Atomic force microscopy as a tool for the investigation of living cells. Medicina (Kaunas) 49:155–164
Sirghi L (2010) Atomic force microscopy indentation of living cells. Microscopy: science, technology. Applications and Education, Formatex, Badajoz, pp. 433–440
Shuman DJ, Costa AL, Andrade MS (2007) Calculating the elastic modulus from nanoindentation and microindentation reload curves. Materials Characterization 58:380–389
Foster B (2012) New atomic force microscopy(afm) approaches life sciences gently, quantitatively, and correctively. Am Lab 44:24–28
Rotsch C, Radmacher M (2000) Drug-induced changes of cytoskeletal structure and mechanics in fibroblasts: an atomic force microscopy study. Biophys J 78:520–535
Sadeghian H, van den Dool TC, Uziel Y, Or RB (2015) High-speed AFM for 1x node metrology and inspection: Does it damage the features? , in Metrology, Inspection, and Process Control for Microlithography XXIX, vol. 9424, p. 94240Q
Schäffer TE, Cleveland JP, Ohnesorge F, Walters DA, Hansma PK (1996) Studies of vibrating atomic force microscope cantilevers in liquid. J Appl Phys 80:3622–3627
Englund R, Palmerius KL, Hotz I, Ynnerman A (2018) Touching data: enhancing visual exploration of flow data with haptics. Comuting in Science & Enginneering, 89–99
Féréol S, Fodil R, Laurent V, Planus E, Louis B, Pelle G, Isabey D (2008) Mechanical and structural assessment of cortical and deep cytoskeleton reveals substrate-dependent alveolar macrophage remodeling. Biomed Mater Eng 18:105–118
Fodil R, Laurent V, Planus E, Isabey D (2003) Characterization of cytoskeleton mechanical properties and 3d-actin structure in twisted adherent epithelial cells. Biorheology 40:241–245
Lecuyer A, Burkhardt JM, Coquillart S, Coiffet P (2001) Boundary of illusion: an experiment of sensory integration with a pseudo-haptic system. In Proceedings of IEEE VR’2001
Acknowledgments
National project FUI - REVE 5D: Réalité Augmentée pour la Culture, les Infrastructures et l’Industrie, University of Lyon, ENISE.
Regional project “Apprentissage Enactif” funding by IDEX (Initiative D’EXcellence) Formation, University of Grenoble Alpes.
CIME Nanotech for AFM support and funding of Claudie Petit for data about the osteoblast cell.
European Research Council (ERC grant biolochanics, grant number 647067) for funding Claudie Petit works on AoSMC cells, EMSE.
Author information
Authors and Affiliations
Corresponding author
Additional information
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Petit, C., Kechiche, M., Ivan, I.A. et al. Visuo-haptic virtual exploration of single cell morphology and mechanics based on AFM mapping in fast mode. J Micro-Bio Robot 16, 147–160 (2020). https://doi.org/10.1007/s12213-020-00140-5
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12213-020-00140-5