Nanoscale imaging and force probing of biomolecular systems using atomic force microscopy: from single molecules to living cells.

Due to the lack of adequate tools for observation, native molecular behaviors at the nanoscale have been poorly understood. The advent of atomic force microscopy (AFM) provides an exciting instrument for investigating physiological processes on individual living cells with molecular resolution, which attracts the attention of worldwide researchers. In the past few decades, AFM has been widely utilized to investigate molecular activities on diverse biological interfaces, and the performances and functions of AFM have also been continuously improved, greatly improving our understanding of the behaviors of single molecules in action and demonstrating the important role of AFM in addressing biological issues with unprecedented spatiotemporal resolution. In this article, we review the related techniques and recent progress about applying AFM to characterize biomolecular systems in situ from single molecules to living cells. The challenges and future directions are also discussed.

[1]  T. Perkins,et al.  Hidden dynamics in the unfolding of individual bacteriorhodopsin proteins , 2017, Science.

[2]  Patrick A. Gerin,et al.  Direct Probing of the Surface Ultrastructure and Molecular Interactions of Dormant and Germinating Spores ofPhanerochaete chrysosporium , 1999, Journal of bacteriology.

[3]  M. Targosz-Korecka,et al.  The impact of hyperglycemia on adhesion between endothelial and cancer cells revealed by single‐cell force spectroscopy , 2017, Journal of molecular recognition : JMR.

[4]  Yuechao Wang,et al.  Imaging and Force Recognition of Single Molecular Behaviors Using Atomic Force Microscopy , 2017, Sensors.

[5]  Jung Hoon Jung,et al.  Visualization and Quantification of MicroRNA in a Single Cell Using Atomic Force Microscopy. , 2016, Journal of the American Chemical Society.

[6]  Li Xu,et al.  Atomic force microscopy study of the effect of HER 2 antibody on EGF mediated ErbB ligand-receptor interaction. , 2013, Nanomedicine : nanotechnology, biology, and medicine.

[7]  Nikolaj Gadegaard,et al.  Harnessing nanotopography and integrin-matrix interactions to influence stem cell fate. , 2014, Nature materials.

[8]  K. V. van Holde,et al.  Linker DNA accessibility in chromatin fibers of different conformations: a reevaluation. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[9]  H. Sieburg,et al.  Stem cell heterogeneity: implications for aging and regenerative medicine. , 2012, Blood.

[10]  J. Hoh,et al.  Slow cellular dynamics in MDCK and R5 cells monitored by time-lapse atomic force microscopy. , 1994, Biophysical journal.

[11]  Patrice Soumillion,et al.  Multiparametric atomic force microscopy imaging of single bacteriophages extruding from living bacteria , 2013, Nature Communications.

[12]  D. Ingber,et al.  Mechanotransduction at a distance: mechanically coupling the extracellular matrix with the nucleus , 2009, Nature Reviews Molecular Cell Biology.

[13]  Daniel J. Muller,et al.  Multiparametric high-resolution imaging of native proteins by force-distance curve–based AFM , 2014, Nature Protocols.

[14]  Use of atomic force microscopy (AFM) to explore cell wall properties and response to stress in the yeast Saccharomyces cerevisiae , 2013, Current Genetics.

[15]  Manfred Radmacher,et al.  Measuring the elastic properties of living cells by the atomic force microscope. , 2002, Methods in cell biology.

[16]  Yves F Dufrêne,et al.  Sticky microbes: forces in microbial cell adhesion. , 2015, Trends in microbiology.

[17]  Mingjun Cai,et al.  The Asymmetrical Structure of Golgi Apparatus Membranes Revealed by In situ Atomic Force Microscope , 2013, PloS one.

[18]  Y. Dufrêne,et al.  Zinc-dependent mechanical properties of Staphylococcus aureus biofilm-forming surface protein SasG , 2015, Proceedings of the National Academy of Sciences.

[19]  J. Colchero,et al.  True non-contact atomic force microscopy imaging of heterogeneous biological samples in liquids: topography and material contrast. , 2017, Nanoscale.

[20]  Daniel J. Muller,et al.  High-resolution atomic force microscopy and spectroscopy of native membrane proteins , 2011 .

[21]  H. Oberleithner,et al.  Feeling for Filaments: Quantification of the Cortical Actin Web in Live Vascular Endothelium , 2015, Biophysical journal.

[22]  Mark J. Ratain,et al.  Tumour heterogeneity in the clinic , 2013, Nature.

[23]  T. Ludwig,et al.  Functional analysis of bispecific antibody (EpCAMxCD3)‐mediated T‐lymphocyte and cancer cell interaction by single‐cell force spectroscopy , 2011, International journal of cancer.

[24]  M. Radmacher,et al.  From molecules to cells: imaging soft samples with the atomic force microscope. , 1992, Science.

[25]  Joan-Ramon Daban,et al.  Electron microscopy and atomic force microscopy studies of chromatin and metaphase chromosome structure. , 2011, Micron.

[26]  T. Schwartz,et al.  The Nuclear Pore Complex as a Flexible and Dynamic Gate , 2016, Cell.

[27]  Lianqing Liu,et al.  Rapid recognition and functional analysis of membrane proteins on human cancer cells using atomic force microscopy. , 2016, Journal of immunological methods.

[28]  A. Beaussart,et al.  Quantifying the forces guiding microbial cell adhesion using single-cell force spectroscopy , 2014, Nature Protocols.

[29]  Yves F. Dufrêne,et al.  Optical and force nanoscopy in microbiology , 2016, Nature Microbiology.

[30]  D. Müller,et al.  Multiparametric imaging of biological systems by force-distance curve–based AFM , 2013, Nature Methods.

[31]  Yves F Dufrêne,et al.  Single-molecule imaging of cell surfaces using near-field nanoscopy. , 2012, Accounts of chemical research.

[32]  B. Druker,et al.  Crosstalk between ROR1 and the Pre-B cell receptor promotes survival of t(1;19) acute lymphoblastic leukemia. , 2012, Cancer cell.

[33]  Hideki Kandori,et al.  High-speed atomic force microscopy shows dynamic molecular processes in photoactivated bacteriorhodopsin. , 2010, Nature nanotechnology.

[34]  Jelena Mandic,et al.  Chemomechanical mapping of ligand–receptor binding kinetics on cells , 2007, Proceedings of the National Academy of Sciences.

[35]  Daniel J. Muller,et al.  Assay for characterizing the recovery of vertebrate cells for adhesion measurements by single‐cell force spectroscopy , 2014, FEBS letters.

[36]  Corbin E. Meacham,et al.  Tumour heterogeneity and cancer cell plasticity , 2013, Nature.

[37]  Yves F Dufrêne,et al.  High-resolution cell surface dynamics of germinating Aspergillus fumigatus conidia. , 2008, Biophysical journal.

[38]  Samy Lamouille,et al.  Molecular mechanisms of epithelial–mesenchymal transition , 2014, Nature Reviews Molecular Cell Biology.

[39]  Peter Hinterdorfer,et al.  Detection of HSP60 on the membrane surface of stressed human endothelial cells by atomic force and confocal microscopy , 2005, Journal of Cell Science.

[40]  F. Kienberger,et al.  A new, simple method for linking of antibodies to atomic force microscopy tips. , 2007, Bioconjugate chemistry.

[41]  T. Ando,et al.  Visualization and structural analysis of the bacterial magnetic organelle magnetosome using atomic force microscopy , 2010, Proceedings of the National Academy of Sciences of the United States of America.

[42]  Peter Hinterdorfer,et al.  Ligands on the string: single-molecule AFM studies on the interaction of antibodies and substrates with the Na+-glucose co-transporter SGLT1 in living cells , 2006, Journal of Cell Science.

[43]  Jens Friedrichs,et al.  Quantifying cellular adhesion to extracellular matrix components by single-cell force spectroscopy , 2010, Nature Protocols.

[44]  S. Lindsay,et al.  Antibody-unfolding and metastable-state binding in force spectroscopy and recognition imaging. , 2011, Biophysical journal.

[45]  Tomaso Zambelli,et al.  Tunable Single-Cell Extraction for Molecular Analyses , 2016, Cell.

[46]  Xin Shang,et al.  Localization of Na+-K+ ATPases in quasi-native cell membranes. , 2009, Nano letters.

[47]  Timothy J. Foster,et al.  Adhesion, invasion and evasion: the many functions of the surface proteins of Staphylococcus aureus , 2013, Nature Reviews Microbiology.

[48]  Yves F. Dufrêne,et al.  Force nanoscopy of living cells , 2011, Current Biology.

[49]  Toshio Ando,et al.  Guide to video recording of structure dynamics and dynamic processes of proteins by high-speed atomic force microscopy , 2012, Nature Protocols.

[50]  Y. Dufrêne,et al.  Molecular interactions and inhibition of the staphylococcal biofilm-forming protein SdrC , 2017, Proceedings of the National Academy of Sciences.

[51]  S. D. De Keersmaecker,et al.  Detection, localization, and conformational analysis of single polysaccharide molecules on live bacteria. , 2008, ACS nano.

[52]  David Alsteens,et al.  Single-molecule imaging and functional analysis of Als adhesins and mannans during Candida albicans morphogenesis. , 2012, ACS nano.

[53]  Stéphane Cuenot,et al.  Nanoscale mapping and functional analysis of individual adhesins on living bacteria , 2005, Nature Methods.

[54]  Vladimir N Uversky,et al.  Nanoimaging for protein misfolding and related diseases , 2006, Journal of cellular biochemistry.

[55]  Daniel J Müller,et al.  Multiparametric Atomic Force Microscopy Imaging of Biomolecular and Cellular Systems. , 2017, Accounts of chemical research.

[56]  Robert H Singer,et al.  Single-Cell and Single-Molecule Analysis of Gene Expression Regulation. , 2016, Annual review of genetics.

[57]  L. Oddershede,et al.  Force probing of individual molecules inside the living cell is now a reality. , 2012, Nature chemical biology.

[58]  Henning Stahlberg,et al.  Structural biology: Proton-powered turbine of a plant motor , 2000, Nature.

[59]  Keir C. Neuman,et al.  SnapShot: Force Spectroscopy and Single-Molecule Manipulation , 2013, Cell.

[60]  Y. Lyubchenko,et al.  Atomic force microscopy of long DNA: imaging in air and under water. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[61]  Y. WANG,et al.  Nanoscale distribution of CD20 on B‐cell lymphoma tumour cells and its potential role in the clinical efficacy of rituximab , 2014, Journal of microscopy.

[62]  V. Shahin,et al.  Aldosterone signaling pathway across the nuclear envelope , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[63]  Kazuhiko Kinosita,et al.  Direct observation of the rotation of F1-ATPase , 1997, Nature.

[64]  C. Gerber,et al.  Imaging modes of atomic force microscopy for application in molecular and cell biology. , 2017, Nature nanotechnology.

[65]  K. Neuman,et al.  Single-molecule force spectroscopy: optical tweezers, magnetic tweezers and atomic force microscopy , 2008, Nature Methods.

[66]  J. Rao,et al.  Nanomechanical analysis of cells from cancer patients. , 2007, Nature nanotechnology.

[67]  Mingjun Cai,et al.  High resolution imaging of mitochondrial membranes by in situ atomic force microscopy , 2013 .

[68]  P. Strappe,et al.  Atomic force microscopy on chromosomes, chromatin and DNA: a review. , 2012, Micron.

[69]  Russell M. Gordley,et al.  Engineering Customized Cell Sensing and Response Behaviors Using Synthetic Notch Receptors , 2016, Cell.

[70]  Hiroyuki Noji,et al.  High-Speed Atomic Force Microscopy Reveals Rotary Catalysis of Rotorless F1-ATPase , 2011, Science.

[71]  S. Scheuring,et al.  Atomic force microscopy: probing the spatial organization, interactions and elasticity of microbial cell envelopes at molecular resolution , 2010, Molecular microbiology.

[72]  Tatsuo Ushiki,et al.  Atomic force microscopy for imaging human metaphase chromosomes , 2008, Chromosome Research.

[73]  Masayuki Endo,et al.  Single-molecule imaging of dynamic motions of biomolecules in DNA origami nanostructures using high-speed atomic force microscopy. , 2014, Accounts of chemical research.

[74]  Lianqing Liu,et al.  Imaging and measuring the rituximab-induced changes of mechanical properties in B-lymphoma cells using atomic force microscopy. , 2011, Biochemical and biophysical research communications.

[75]  Zbigniew Stachura,et al.  Cancer cell detection in tissue sections using AFM. , 2012, Archives of biochemistry and biophysics.

[76]  N. McGranahan,et al.  The causes and consequences of genetic heterogeneity in cancer evolution , 2013, Nature.

[77]  T. Ando,et al.  High-speed atomic force microscopy imaging of live mammalian cells , 2017, Biophysics and physicobiology.

[78]  Y. Dufrêne,et al.  Single-Cell and Single-Molecule Analysis Unravels the Multifunctionality of the Staphylococcus aureus Collagen-Binding Protein Cna. , 2017, ACS nano.

[79]  A. Engel,et al.  Adsorption of biological molecules to a solid support for scanning probe microscopy. , 1997, Journal of structural biology.

[80]  G. G. Stokes "J." , 1890, The New Yale Book of Quotations.

[81]  Lianqing Liu,et al.  Drug-Induced Changes of Topography and Elasticity in Living B Lymphoma Cells Based on Atomic Force Microscopy , 2012 .

[82]  Lucas Pelkmans,et al.  Using Cell-to-Cell Variability—A New Era in Molecular Biology , 2012, Science.

[83]  H. Gaub,et al.  Unfolding pathways of individual bacteriorhodopsins. , 2000, Science.

[84]  D. Maloney Anti-CD20 antibody therapy for B-cell lymphomas. , 2012, The New England journal of medicine.

[85]  D. Lohr,et al.  Single-molecule recognition imaging microscopy. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[86]  Lianqing Liu,et al.  Nanoscale mapping and organization analysis of target proteins on cancer cells from B-cell lymphoma patients. , 2013, Experimental cell research.

[87]  Jing Zhang,et al.  Nanoscale organization of human GnRH-R on human bladder cancer cells. , 2014, Analytical chemistry.

[88]  Toshio Ando,et al.  Filming Biomolecular Processes by High-Speed Atomic Force Microscopy , 2014, Chemical reviews.

[89]  Andreas Ebner,et al.  IgGs are made for walking on bacterial and viral surfaces , 2014, Nature Communications.

[90]  Guillaume Andre,et al.  Imaging the nanoscale organization of peptidoglycan in living Lactococcus lactis cells , 2010, Nature communications.

[91]  Lianqing Liu,et al.  AFM analysis of the multiple types of molecular interactions involved in rituximab lymphoma therapy on patient tumor cells and NK cells. , 2014, Cellular immunology.

[92]  Andreas Ebner,et al.  Simultaneous topography and recognition imaging using force microscopy. , 2004, Biophysical journal.

[93]  G. Charras,et al.  The cytoplasm of living cells behaves as a poroelastic material , 2013, Nature materials.

[94]  Stavroula Skylaki,et al.  Challenges in long-term imaging and quantification of single-cell dynamics , 2016, Nature Biotechnology.

[95]  P. Gavazzo,et al.  Probing cytoskeleton organisation of neuroblastoma cells with single‐cell force spectroscopy , 2012, Journal of molecular recognition : JMR.

[96]  Jilin Tang,et al.  Single molecular recognition force spectroscopy study of a luteinizing hormone-releasing hormone analogue as a carcinoma target drug. , 2012, The journal of physical chemistry. B.

[97]  S. Scheuring,et al.  Atomic force microscopy of the bacterial photosynthetic apparatus: plain pictures of an elaborate machinery , 2009, Photosynthesis Research.

[98]  Ericka Stricklin-Parker,et al.  Ann , 2005 .

[99]  Evan Evans,et al.  Five challenges to bringing single-molecule force spectroscopy into living cells , 2011, Nature Methods.

[100]  Toshio Ando,et al.  Video imaging of walking myosin V by high-speed atomic force microscopy , 2010, Nature.

[101]  Sheng Yao,et al.  Advances in targeting cell surface signalling molecules for immune modulation , 2013, Nature Reviews Drug Discovery.

[102]  J. Pelta,et al.  Elasticity, Adhesion, and Tether Extrusion on Breast Cancer Cells Provide a Signature of Their Invasive Potential. , 2016, ACS applied materials & interfaces.

[103]  Alan M. Jones,et al.  Cell Surface ABP1-TMK Auxin-Sensing Complex Activates ROP GTPase Signaling , 2014, Science.

[104]  X. Xie,et al.  Single-cell whole-genome analyses by Linear Amplification via Transposon Insertion (LIANTI) , 2017, Science.

[105]  A. Beaussart,et al.  Forces in yeast flocculation. , 2015, Nanoscale.

[106]  H. Gaub,et al.  Adhesion forces between individual ligand-receptor pairs. , 1994, Science.

[107]  Giovanni Dietler,et al.  Time-lapse AFM imaging of DNA conformational changes induced by daunorubicin. , 2013, Nano letters.

[108]  M. Radmacher,et al.  Substrate dependent differences in morphology and elasticity of living osteoblasts investigated by atomic force microscopy. , 2000, Colloids and surfaces. B, Biointerfaces.

[109]  Simon Scheuring,et al.  Chromatic Adaptation of Photosynthetic Membranes , 2005, Science.

[110]  Robert G. Parton,et al.  Caveolae as plasma membrane sensors, protectors and organizers , 2013, Nature Reviews Molecular Cell Biology.

[111]  Daniel J Müller,et al.  Atomic force microscopy as a multifunctional molecular toolbox in nanobiotechnology. , 2008, Nature nanotechnology.

[112]  Daniel J Müller,et al.  Atomic force microscopy and spectroscopy of native membrane proteins , 2007, Nature Protocols.

[113]  Delyan R. Hristov,et al.  Mapping of Molecular Structure of the Nanoscale Surface in Bionanoparticles. , 2017, Journal of the American Chemical Society.

[114]  Lianqing Liu,et al.  Progress of AFM single-cell and single-molecule morphology imaging , 2013 .

[115]  Daniel J. Muller,et al.  Single-cell force spectroscopy , 2008, Journal of Cell Science.

[116]  Ueli Aebi,et al.  The nanomechanical signature of breast cancer. , 2012, Nature nanotechnology.

[117]  Daniel J Müller,et al.  Deciphering molecular interactions of native membrane proteins by single-molecule force spectroscopy. , 2007, Annual review of biophysics and biomolecular structure.

[118]  Daniel J Müller,et al.  Force probing surfaces of living cells to molecular resolution. , 2009, Nature chemical biology.

[119]  Peter Hinterdorfer,et al.  Single-molecule recognition force spectroscopy of transmembrane transporters on living cells , 2011, Nature Protocols.

[120]  I. Ford,et al.  Nanoscale stiffness topography reveals structure and mechanics of the transport barrier in intact nuclear pore complexes , 2014, Nature nanotechnology.

[121]  R. Metzler,et al.  Manipulation and Motion of Organelles and Single Molecules in Living Cells. , 2017, Chemical reviews.

[122]  A. Beaussart,et al.  Single-cell force spectroscopy of pili-mediated adhesion. , 2014, Nanoscale.

[123]  Masasuke Yoshida,et al.  Mechanical modulation of catalytic power on F1-ATPase. , 2011, Nature chemical biology.

[124]  A. Beaussart,et al.  Single-cell force spectroscopy of probiotic bacteria. , 2013, Biophysical journal.

[125]  Daniel A. Fletcher,et al.  Combined atomic force microscopy and side-view optical imaging for mechanical studies of cells , 2009, Nature Methods.

[126]  Mark Bates,et al.  Three-Dimensional Super-Resolution Imaging by Stochastic Optical Reconstruction Microscopy , 2008, Science.

[127]  Yves F Dufrêne,et al.  Single-Cell Force Spectroscopy of Als-Mediated Fungal Adhesion. , 2013, Analytical methods : advancing methods and applications.

[128]  D. Müller,et al.  Single-molecule force spectroscopy of membrane proteins from membranes freely spanning across nanoscopic pores. , 2015, Nano letters.

[129]  Carsten Werner,et al.  A practical guide to quantify cell adhesion using single-cell force spectroscopy. , 2013, Methods.

[130]  Roderick Y. H. Lim,et al.  Spatiotemporal dynamics of the nuclear pore complex transport barrier resolved by high-speed atomic force microscopy. , 2016, Nature nanotechnology.

[131]  Siewert J Marrink,et al.  Mechanisms shaping cell membranes. , 2014, Current opinion in cell biology.

[132]  Henning Stahlberg,et al.  Characterization of the motion of membrane proteins using high-speed atomic force microscopy. , 2012, Nature nanotechnology.

[133]  Lianqing Liu,et al.  Quantitative Analysis of Drug-Induced Complement-Mediated Cytotoxic Effect on Single Tumor Cells Using Atomic Force Microscopy and Fluorescence Microscopy , 2015, IEEE Transactions on NanoBioscience.

[134]  E. Betzig,et al.  Imaging live-cell dynamics and structure at the single-molecule level. , 2015, Molecular cell.

[135]  H. Sitte,et al.  Probing Binding Pocket of Serotonin Transporter by Single Molecular Force Spectroscopy on Living Cells* , 2011, The Journal of Biological Chemistry.

[136]  Flavien Pillet,et al.  Generation of living cell arrays for atomic force microscopy studies , 2014, Nature Protocols.

[137]  M. Mooseker,et al.  Myosins: tails (and heads) of functional diversity. , 2005, Physiology.

[138]  S. Scheuring,et al.  Forces guiding assembly of light-harvesting complex 2 in native membranes , 2011, Proceedings of the National Academy of Sciences.

[139]  A. Beaussart,et al.  Force nanoscopy of hydrophobic interactions in the fungal pathogen Candida glabrata. , 2015, ACS nano.

[140]  John A. Hammer,et al.  Walking to work: roles for class V myosins as cargo transporters , 2011, Nature Reviews Molecular Cell Biology.

[141]  Cees Dekker,et al.  High-Speed AFM Reveals the Dynamics of Single Biomolecules at the Nanometer Scale , 2011, Cell.

[142]  R Lemor,et al.  Cell specific ultrasound effects are dose and frequency dependent. , 2013, Annals of anatomy = Anatomischer Anzeiger : official organ of the Anatomische Gesellschaft.

[143]  J. Workman,et al.  Histone exchange, chromatin structure and the regulation of transcription , 2015, Nature Reviews Molecular Cell Biology.

[144]  Toshio Ando,et al.  Single-molecule imaging on living bacterial cell surface by high-speed AFM. , 2012, Journal of molecular biology.

[145]  Kuo-Kang Liu,et al.  Quantifying cellular mechanics and adhesion in renal tubular injury using single cell force spectroscopy. , 2016, Nanomedicine : nanotechnology, biology, and medicine.

[146]  Y. Dufrêne,et al.  Nanoscale adhesion forces between the fungal pathogen Candida albicans and macrophages. , 2016, Nanoscale horizons.

[147]  Simon Scheuring,et al.  Structural, mechanical, and dynamical variability of the actin cortex in living cells. , 2015, Biophysical journal.

[148]  Daniel J. Müller,et al.  Out but not in: the large transmembrane β-barrel protein FhuA unfolds but cannot refold via β-hairpins. , 2012, Structure.

[149]  N. Santos,et al.  Atomic force microscopy-based molecular recognition of a fibrinogen receptor on human erythrocytes. , 2010, ACS nano.

[150]  Y. Lyubchenko,et al.  Nanoprobing of α-synuclein misfolding and aggregation with atomic force microscopy. , 2011, Nanomedicine : nanotechnology, biology, and medicine.

[151]  H. Gaub,et al.  Membrane proteins scrambling through a folding landscape , 2017, Science.

[152]  C. Hunter,et al.  Direct Imaging of Protein Organization in an Intact Bacterial Organelle Using High-Resolution Atomic Force Microscopy , 2016, ACS nano.

[153]  Lin Yu,et al.  Matrix Stiffness and Nanoscale Spatial Organization of Cell-Adhesive Ligands Direct Stem Cell Fate. , 2015, Nano letters.

[154]  Shuiqing Hu,et al.  PeakForce Tapping resolves individual microvilli on living cells† , 2015, Journal of molecular recognition : JMR.

[155]  Daniel J Müller,et al.  Deciphering teneurin domains that facilitate cellular recognition, cell-cell adhesion, and neurite outgrowth using atomic force microscopy-based single-cell force spectroscopy. , 2013, Nano letters.

[156]  M. Niepel,et al.  The nuclear pore complex: bridging nuclear transport and gene regulation , 2010, Nature Reviews Molecular Cell Biology.

[157]  Yves F Dufrêne,et al.  Force-induced formation and propagation of adhesion nanodomains in living fungal cells , 2010, Proceedings of the National Academy of Sciences.

[158]  Manel Puig-Vidal,et al.  High-Speed Force Spectroscopy Unfolds Titin at the Velocity of Molecular Dynamics Simulations , 2013, Science.

[159]  Daniel A Fletcher,et al.  Force microscopy of nonadherent cells: a comparison of leukemia cell deformability. , 2006, Biophysical journal.

[160]  Paul A. Wiggins,et al.  Emerging roles for lipids in shaping membrane-protein function , 2009, Nature.

[161]  M. Cragg,et al.  Mechanisms of killing by anti-CD20 monoclonal antibodies. , 2007, Molecular immunology.

[162]  A. Engel,et al.  Atomic-force microscopy: Rhodopsin dimers in native disc membranes , 2003, Nature.

[163]  S. Mayor,et al.  The mystery of membrane organization: composition, regulation and roles of lipid rafts , 2017, Nature Reviews Molecular Cell Biology.

[164]  Simon Scheuring,et al.  Investigation of photosynthetic membrane structure using atomic force microscopy. , 2013, Trends in plant science.

[165]  Lianqing Liu,et al.  Atomic force microscopy study of the antigen‐antibody binding force on patient cancer cells based on ROR1 fluorescence recognition , 2013, Journal of molecular recognition : JMR.

[166]  N. Santos,et al.  Atomic force microscopy as a tool to evaluate the risk of cardiovascular diseases in patients. , 2016, Nature nanotechnology.

[167]  Christophe Chipot,et al.  High-speed atomic force microscopy shows that annexin V stabilizes membranes on the second timescale. , 2016, Nature nanotechnology.

[168]  K. Pantel,et al.  Challenges in circulating tumour cell research , 2014, Nature Reviews Cancer.

[169]  Xiaohong Fang,et al.  Single-molecule force spectroscopy study of interaction between transforming growth factor beta1 and its receptor in living cells. , 2007, The journal of physical chemistry. B.

[170]  T. Ando,et al.  Dynamics of nucleosomes assessed with time-lapse high-speed atomic force microscopy. , 2011, Biochemistry.

[171]  H. Hansma Surface biology of DNA by atomic force microscopy. , 2001, Annual review of physical chemistry.

[172]  J. Sturgis,et al.  Atomic force microscopy studies of native photosynthetic membranes. , 2009, Biochemistry.

[173]  Kai Simons,et al.  Lipid Rafts As a Membrane-Organizing Principle , 2010, Science.

[174]  Yves F Dufrêne,et al.  The yeast Wsc1 cell surface sensor behaves like a nanospring in vivo. , 2009, Nature chemical biology.

[175]  Georg E. Fantner,et al.  Kinetics of Antimicrobial Peptide Activity Measured on Individual Bacterial Cells Using High Speed AFM , 2010, Nature nanotechnology.

[176]  P. Hinterdorfer,et al.  Localization of the ergtoxin-1 receptors on the voltage sensing domain of hERG K+ channel by AFM recognition imaging , 2008, Pflügers Archiv - European Journal of Physiology.

[177]  S. Lindsay,et al.  Recent Progress in Molecular Recognition Imaging Using Atomic Force Microscopy. , 2016, Accounts of chemical research.

[178]  C. Dobson Protein folding and misfolding , 2003, Nature.

[179]  F. Rico,et al.  High-speed atomic force microscopy: Structure and dynamics of single proteins. , 2011, Current opinion in chemical biology.

[180]  Toshio Ando,et al.  High-speed AFM imaging. , 2014, Current opinion in structural biology.

[181]  Gang Zhao,et al.  Nanotopographical Surfaces for Stem Cell Fate Control: Engineering Mechanobiology from the Bottom. , 2014, Nano today.

[182]  M. Davidson,et al.  Nanoscale architecture of cadherin-based cell adhesions , 2016, Nature Cell Biology.

[183]  Botond Roska,et al.  Nanomechanical mapping of first binding steps of a virus to animal cells. , 2017, Nature nanotechnology.

[184]  H. Gong,et al.  The effect of the endothelial cell cortex on atomic force microscopy measurements. , 2013, Biophysical journal.

[185]  Yves F Dufrêne,et al.  Atomic force microscopy and chemical force microscopy of microbial cells , 2008, Nature Protocols.

[186]  N. Santos,et al.  Atomic force microscopy‐based force spectroscopy — biological and biomedical applications , 2012, IUBMB life.

[187]  H Schindler,et al.  Detection and localization of individual antibody-antigen recognition events by atomic force microscopy. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[188]  Andreas Ebner,et al.  Linking of Sensor Molecules with Amino Groups to Amino-Functionalized AFM Tips , 2011, Bioconjugate chemistry.

[189]  Y. Lyubchenko Preparation of DNA and nucleoprotein samples for AFM imaging. , 2011, Micron.

[190]  N. Xi,et al.  The dynamic interactions between chemotherapy drugs and plasmid DNA investigated by atomic force microscopy , 2017, Science China Materials.

[191]  Aiko Yoshida,et al.  Probing in vivo dynamics of mitochondria and cortical actin networks using high‐speed atomic force/fluorescence microscopy , 2015, Genes to cells : devoted to molecular & cellular mechanisms.

[192]  Philip P. LeDuc,et al.  Nanoscale Intracellular Organization and Functional Architecture Mediating Cellular Behavior , 2006, Annals of Biomedical Engineering.

[193]  P. Reynolds,et al.  Protein Adsorption as a Key Mediator in the Nanotopographical Control of Cell Behavior , 2016, ACS nano.

[194]  Yuechao Wang,et al.  Nanoscale Quantifying the Effects of Targeted Drug on Chemotherapy in Lymphoma Treatment Using Atomic Force Microscopy , 2016, IEEE Transactions on Biomedical Engineering.

[195]  Y. Dufrêne,et al.  Detection and localization of single molecular recognition events using atomic force microscopy , 2006, Nature Methods.

[196]  Mi Li,et al.  Atomic force microscopy imaging of live mammalian cells , 2013, Science China Life Sciences.

[197]  G. Hummer,et al.  Phosphate release coupled to rotary motion of F1-ATPase , 2013, Proceedings of the National Academy of Sciences.

[198]  P. Haydon,et al.  Actin filament dynamics in living glial cells imaged by atomic force microscopy. , 1992, Science.

[199]  Yves F Dufrêne,et al.  In vivo imaging of S-layer nanoarrays on Corynebacterium glutamicum. , 2009, Langmuir : the ACS journal of surfaces and colloids.

[200]  Daniel J Müller,et al.  Atomic force microscopy: a nanoscopic window on the cell surface. , 2011, Trends in cell biology.

[201]  Yaron E. Antebi,et al.  Dynamics of epigenetic regulation at the single-cell level , 2016, Science.