Studying structure and functions of cell membranes by single molecule biophysical techniques

Cell membranes are complicated multicomponent structures, related to many basic cellular processes, such as substance transporting, energy conversion, signal transduction, mechanosensing, cell adhesion and so on. However, cell membranes have long been difficult to study at a single-molecule level due to their complex and dynamic properties. During the last decades, biophysical imaging techniques, such as atomic force microscopy and super-resolution fluorescent microscopy, have been developed to study biological structures with unprecedented resolution, enabling researchers to analyze the composition and distribution of membrane proteins and monitor their specific functions at single cell/molecule level. In this review, we highlight the structure and functions of cell membranes based on up-to-date biophysical techniques. Additionally, we describe the recent advances in force-based detecting technology, which allow insight into dynamic events and quantitativelymonitoring kinetic parameters for trans-membrane transporting in living cells.

[1]  C. Karathanasis,et al.  Single-molecule imaging and quantification of the immune-variant adhesin VAR2CSA on knobs of Plasmodium falciparum-infected erythrocytes , 2019, Communications Biology.

[2]  Ken Jacobson,et al.  The Lateral Organization and Mobility of Plasma Membrane Components , 2019, Cell.

[3]  Guocheng Yang,et al.  Monitoring the trans-membrane transport of single fluorescent silicon nanoparticles based on the force tracing technique , 2019, Analytical Methods.

[4]  C. Gerle Essay on Biomembrane Structure , 2019, The Journal of Membrane Biology.

[5]  M. Trepel,et al.  Differential organization of tonic and chronic B cell antigen receptors in the plasma membrane , 2019, Nature Communications.

[6]  Guocheng Yang,et al.  Tracking the Single-Carbon-Dot Transmembrane Transport by Force Tracing Based on Atomic Force Microscopy. , 2019, ACS biomaterials science & engineering.

[7]  C. Bertozzi,et al.  Quantitative Super-Resolution Microscopy of the Mammalian Glycocalyx. , 2018, Developmental cell.

[8]  Hongda Wang,et al.  Single glucose molecule transport process revealed by force tracing and molecular dynamics simulations. , 2018, Nanoscale horizons.

[9]  D. Alsteens,et al.  Multivalent binding of herpesvirus to living cells is tightly regulated during infection , 2018, Science Advances.

[10]  Yan Shi,et al.  Mechanistic insights into GLUT1 activation and clustering revealed by super-resolution imaging , 2018, Proceedings of the National Academy of Sciences.

[11]  Athanasios Sideris,et al.  Dynamic lateral organization of opioid receptors (kappa, muwt and muN40D) in the plasma membrane at the nanoscale level , 2018, Traffic.

[12]  Mingjun Cai,et al.  Exploring the trans-membrane dynamic mechanisms of single polyamidoamine nano-drugs via a “force tracing” technique , 2018, RSC advances.

[13]  S. Hell,et al.  Fluorescence nanoscopy in cell biology , 2017, Nature Reviews Molecular Cell Biology.

[14]  Emily A. Smith,et al.  Raman Imaging in Cell Membranes, Lipid-Rich Organelles, and Lipid Bilayers. , 2017, Annual review of analytical chemistry.

[15]  Mingjun Cai,et al.  The Process of Wrapping Virus Revealed by a Force Tracing Technique and Simulations , 2017, Advanced science.

[16]  A. Mezzetti,et al.  Time-resolved infrared spectroscopy in the study of photosynthetic systems , 2017, Photosynthesis Research.

[17]  Hongda Wang,et al.  Super-resolution microscopy reveals the insulin-resistance-regulated reorganization of GLUT4 on plasma membranes , 2017, Journal of Cell Science.

[18]  Valeria De Matteis,et al.  Atomic force microscopy combined with optical microscopy for cells investigation , 2017, Microscopy research and technique.

[19]  Mingjun Cai,et al.  Studying the dynamic mechanism of transporting a single drug carrier-polyamidoamine dendrimer through cell membranes by force tracing. , 2016, Nanoscale.

[20]  M. Sauer,et al.  Super-Resolution Imaging of Plasma Membrane Proteins with Click Chemistry , 2016, Front. Cell Dev. Biol..

[21]  P. Rosenthal,et al.  Cryomicroscopy provides structural snapshots of influenza virus membrane fusion , 2016, Nature Structural &Molecular Biology.

[22]  Mingjun Cai,et al.  Systemic localization of seven major types of carbohydrates on cell membranes by dSTORM imaging , 2016, Scientific Reports.

[23]  E. London,et al.  The Effect of Membrane Lipid Composition on the Formation of Lipid Ultrananodomains. , 2015, Biophysical journal.

[24]  Kutti R Vinothkumar,et al.  Membrane protein structures without crystals, by single particle electron cryomicroscopy , 2015, Current opinion in structural biology.

[25]  Jim A. Thomas Optical imaging probes for biomolecules: an introductory perspective. , 2015, Chemical Society reviews.

[26]  Min Zhang,et al.  Ultrafast Tracking of a Single Live Virion During the Invagination of a Cell Membrane. , 2015, Small.

[27]  Yuping Shan,et al.  The structure and function of cell membranes examined by atomic force microscopy and single-molecule force spectroscopy. , 2015, Chemical Society reviews.

[28]  S. Hell,et al.  Lens-based fluorescence nanoscopy , 2015, Quarterly Reviews of Biophysics.

[29]  Mingjun Cai,et al.  Recording the dynamic endocytosis of single gold nanoparticles by AFM-based force tracing. , 2015, Nanoscale.

[30]  Hongbin Ji,et al.  Mechanistic insights into EGFR membrane clustering revealed by super-resolution imaging. , 2015, Nanoscale.

[31]  Ken Jacobson,et al.  Nanoclustering as a dominant feature of plasma membrane organization , 2014, Journal of Cell Science.

[32]  M. Sauer,et al.  Super-resolution imaging of plasma membrane glycans. , 2014, Angewandte Chemie.

[33]  Mingjun Cai,et al.  Studying the membrane structure of chicken erythrocytes by in situ atomic force microscopy , 2014 .

[34]  Síle Nic Chormaic,et al.  Higher order microfibre modes for dielectric particle trapping and propulsion , 2014, Scientific Reports.

[35]  Mingjun Cai,et al.  Atomic Force Microscopy of Asymmetric Membranes from Turtle Erythrocytes , 2014, Molecules and cells.

[36]  Hongbin Ji,et al.  Regulation of EGFR nanocluster formation by ionic protein-lipid interaction , 2014, Cell Research.

[37]  G. Nicolson,et al.  The Fluid-Mosaic Model of Membrane Structure: still relevant to understanding the structure, function and dynamics of biological membranes after more than 40 years. , 2014, Biochimica et biophysica acta.

[38]  F. Goñi,et al.  The basic structure and dynamics of cell membranes: an update of the Singer-Nicolson model. , 2014, Biochimica et biophysica acta.

[39]  Mingjun Cai,et al.  Studying the Nucleated Mammalian Cell Membrane by Single Molecule Approaches , 2014, PloS one.

[40]  Mingjun Cai,et al.  The asymmetric membrane structure of erythrocytes from Crucian carp studied by atomic force microscopy , 2014 .

[41]  J. Staško,et al.  Techniques in Electron Microscopy of Animal Tissue , 2014, Veterinary pathology.

[42]  Mingjun Cai,et al.  High-efficiency localization of Na(+)-K(+) ATPases on the cytoplasmic side by direct stochastic optical reconstruction microscopy. , 2013, Nanoscale.

[43]  Francesco S Pavone,et al.  Interrogating biology with force: single molecule high-resolution measurements with optical tweezers. , 2013, Biophysical journal.

[44]  Travis J Gould,et al.  Actin mediates the nanoscale membrane organization of the clustered membrane protein influenza hemagglutinin. , 2013, Biophysical journal.

[45]  Say Chye Joachim Loo,et al.  Biophysical responses upon the interaction of nanomaterials with cellular interfaces. , 2013, Accounts of chemical research.

[46]  Graça Raposo,et al.  Extracellular vesicles: Exosomes, microvesicles, and friends , 2013, The Journal of cell biology.

[47]  Yao He,et al.  Silicon-nanowire-based nanocarriers with ultrahigh drug-loading capacity for in vitro and in vivo cancer therapy. , 2013, Angewandte Chemie.

[48]  Kenneth A Dawson,et al.  Nanoparticle adhesion to the cell membrane and its effect on nanoparticle uptake efficiency. , 2013, Journal of the American Chemical Society.

[49]  Prabuddha Sengupta,et al.  Visualizing cell structure and function with point-localization superresolution imaging. , 2012, Developmental cell.

[50]  Helmut Grubmüller,et al.  Influenza virus binds its host cell using multiple dynamic interactions , 2012, Proceedings of the National Academy of Sciences.

[51]  R. Balaban,et al.  Role of mitochondrial Ca2+ in the regulation of cellular energetics. , 2012, Biochemistry.

[52]  P. Annibale,et al.  Cell Type-specific β2-Adrenergic Receptor Clusters Identified Using Photoactivated Localization Microscopy Are Not Lipid Raft Related, but Depend on Actin Cytoskeleton Integrity* , 2012, The Journal of Biological Chemistry.

[53]  J. J. Macklin,et al.  Nonlinear structured-illumination microscopy with a photoswitchable protein reveals cellular structures at 50-nm resolution , 2011, Proceedings of the National Academy of Sciences.

[54]  Suliana Manley,et al.  Functional nanoscale organization of signaling molecules downstream of the T cell antigen receptor. , 2011, Immunity.

[55]  O. Mouritsen Lipidology and lipidomics--quo vadis? A new era for the physical chemistry of lipids. , 2011, Physical chemistry chemical physics : PCCP.

[56]  Hayder Amin,et al.  Membrane protein sequestering by ionic protein-lipid interactions , 2011, Nature.

[57]  X. Zhuang,et al.  Breaking the Diffraction Barrier: Super-Resolution Imaging of Cells , 2010, Cell.

[58]  Frederick A. Heberle,et al.  Comparison of three ternary lipid bilayer mixtures: FRET and ESR reveal nanodomains. , 2010, Biophysical journal.

[59]  Thomas S van Zanten,et al.  Direct mapping of nanoscale compositional connectivity on intact cell membranes , 2010, Proceedings of the National Academy of Sciences.

[60]  Steven Chu,et al.  Subnanometre single-molecule localization, registration and distance measurements , 2010, Nature.

[61]  Xin Shang,et al.  Locating the Band III protein in quasi-native cell membranes , 2010 .

[62]  Suliana Manley,et al.  Superresolution imaging using single-molecule localization. , 2010, Annual review of physical chemistry.

[63]  Mingjun Cai,et al.  Preparation of cell membranes for high resolution imaging by AFM. , 2010, Ultramicroscopy.

[64]  M. Veit,et al.  FLIM-FRET and FRAP reveal association of influenza virus haemagglutinin with membrane rafts. , 2010, The Biochemical journal.

[65]  S. Hell,et al.  Stimulated emission depletion nanoscopy of living cells using SNAP-tag fusion proteins. , 2010, Biophysical journal.

[66]  Thomas S van Zanten,et al.  Hotspots of GPI-anchored proteins and integrin nanoclusters function as nucleation sites for cell adhesion , 2009, Proceedings of the National Academy of Sciences.

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

[68]  M. Gustafsson,et al.  Subdiffraction resolution in continuous samples , 2009 .

[69]  Nynke H Dekker,et al.  Quantitative modeling and optimization of magnetic tweezers. , 2009, Biophysical journal.

[70]  Mark Bates,et al.  Super-resolution fluorescence microscopy. , 2009, Annual review of biochemistry.

[71]  H. McMahon,et al.  Mechanisms of endocytosis. , 2009, Annual review of biochemistry.

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

[73]  I. Rodriguez,et al.  Formyl peptide receptor-like proteins are a novel family of vomeronasal chemosensors , 2009, Nature.

[74]  T. Fujimoto,et al.  Segregation of GM1 and GM3 clusters in the cell membrane depends on the intact actin cytoskeleton. , 2009, Biochimica et biophysica acta.

[75]  F. Kienberger,et al.  Multiple receptors involved in human rhinovirus attachment to live cells , 2008, Proceedings of the National Academy of Sciences.

[76]  Yves F. Dufrêne,et al.  Towards nanomicrobiology using atomic force microscopy , 2008, Nature Reviews Microbiology.

[77]  M. Heilemann,et al.  Subdiffraction-resolution fluorescence imaging with conventional fluorescent probes. , 2008, Angewandte Chemie.

[78]  Kuo-Kang Liu,et al.  Optical tweezers for single cells , 2008, Journal of The Royal Society Interface.

[79]  M. Gustafsson,et al.  Subdiffraction Multicolor Imaging of the Nuclear Periphery with 3D Structured Illumination Microscopy , 2008, Science.

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

[81]  Chris Smith,et al.  Molecular Biology of the Cell (Fifth Edition) , 2008 .

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

[83]  E. Betzig,et al.  Live-cell photoactivated localization microscopy of nanoscale adhesion dynamics , 2008, Nature Methods.

[84]  Richard A Strugnell,et al.  Spatially resolved force spectroscopy of bacterial surfaces using force-volume imaging. , 2008, Colloids and surfaces. B, Biointerfaces.

[85]  L. Vigh,et al.  Membranes: a meeting point for lipids, proteins and therapies , 2008, Journal of cellular and molecular medicine.

[86]  J. Lippincott-Schwartz,et al.  High-density mapping of single-molecule trajectories with photoactivated localization microscopy , 2008, Nature Methods.

[87]  Michael W. Davidson,et al.  Dual-color superresolution imaging of genetically expressed probes within individual adhesion complexes , 2007, Proceedings of the National Academy of Sciences.

[88]  Ben Fabry,et al.  High-force magnetic tweezers with force feedback for biological applications. , 2007, The Review of scientific instruments.

[89]  Samuel T. Hess,et al.  Dynamic clustered distribution of hemagglutinin resolved at 40 nm in living cell membranes discriminates between raft theories , 2007, Proceedings of the National Academy of Sciences.

[90]  Thomas Schmidt,et al.  Single-molecule imaging of the H-ras membrane-anchor reveals domains in the cytoplasmic leaflet of the cell membrane. , 2007, Biophysical journal.

[91]  Jan M. Anderson Thylakoid membrane landscape in the sixties: a tribute to Andrew Benson , 2007, Photosynthesis Research.

[92]  E. Isacoff,et al.  Subunit counting in membrane-bound proteins , 2007, Nature Methods.

[93]  S. Hell,et al.  Nanoscale organization of nicotinic acetylcholine receptors revealed by stimulated emission depletion microscopy , 2007, Neuroscience.

[94]  R. Hochstrasser,et al.  Wide-field subdiffraction imaging by accumulated binding of diffusing probes , 2006, Proceedings of the National Academy of Sciences.

[95]  Bridget S. Wilson,et al.  Plasma membrane-associated proteins are clustered into islands attached to the cytoskeleton , 2006, Proceedings of the National Academy of Sciences.

[96]  Michael D. Mason,et al.  Ultra-high resolution imaging by fluorescence photoactivation localization microscopy. , 2006, Biophysical journal.

[97]  Michael J Rust,et al.  Sub-diffraction-limit imaging by stochastic optical reconstruction microscopy (STORM) , 2006, Nature Methods.

[98]  Y. Teramura,et al.  Single‐molecule analysis of epidermal growth factor binding on the surface of living cells , 2006, EMBO Journal.

[99]  J. Lippincott-Schwartz,et al.  Imaging Intracellular Fluorescent Proteins at Nanometer Resolution , 2006, Science.

[100]  F. Ritort,et al.  Methods and Applications , 2006 .

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

[102]  X. Xie,et al.  Living Cells as Test Tubes , 2006, Science.

[103]  T. Yanagida,et al.  Formation of signal transduction complexes during immobile phase of NGFR movements. , 2006, Biochemical and biophysical research communications.

[104]  Russell M. Taylor,et al.  Thin-foil magnetic force system for high-numerical-aperture microscopy. , 2006, The Review of scientific instruments.

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

[106]  T. Yanagida,et al.  Trafficking of a Ligand-Receptor Complex on the Growth Cones as an Essential Step for the Uptake of Nerve Growth Factor at the Distal End of the Axon: A Single-Molecule Analysis , 2005, The Journal of Neuroscience.

[107]  Jie Yan,et al.  Near-field-magnetic-tweezer manipulation of single DNA molecules. , 2004, Physical review. E, Statistical, nonlinear, and soft matter physics.

[108]  Raimundo Gargallo,et al.  Application of multivariate resolution methods to the study of biochemical and biophysical processes. , 2004, Analytical biochemistry.

[109]  J. Konopka,et al.  A Microdomain Formed by the Extracellular Ends of the Transmembrane Domains Promotes Activation of the G Protein-Coupled α-Factor Receptor , 2004, Molecular and Cellular Biology.

[110]  Ira,et al.  Nanoscale Organization of Multiple GPI-Anchored Proteins in Living Cell Membranes , 2004, Cell.

[111]  Paul R. Selvin,et al.  Myosin V Walks Hand-Over-Hand: Single Fluorophore Imaging with 1.5-nm Localization , 2003, Science.

[112]  M. Cadene,et al.  X-ray structure of a voltage-dependent K+ channel , 2003, Nature.

[113]  W E Moerner,et al.  Translational diffusion of individual class II MHC membrane proteins in cells. , 2002, Biophysical journal.

[114]  Charlie Gosse,et al.  Magnetic tweezers: micromanipulation and force measurement at the molecular level. , 2002, Biophysical journal.

[115]  C. Niemeyer REVIEW Nanoparticles, Proteins, and Nucleic Acids: Biotechnology Meets Materials Science , 2022 .

[116]  G. A. Blab,et al.  Single-molecule imaging of l-type Ca(2+) channels in live cells. , 2001, Biophysical journal.

[117]  M. Edidin Near‐Field Scanning Optical Microscopy, a Siren Call to Biology , 2001, Traffic.

[118]  T. Yanagida,et al.  Single-Molecule Analysis of Chemotactic Signaling in Dictyostelium Cells , 2001, Science.

[119]  A Kusumi,et al.  Single molecule imaging of green fluorescent proteins in living cells: E-cadherin forms oligomers on the free cell surface. , 2001, Biophysical journal.

[120]  Denis Wirtz,et al.  Magnetic tweezers for DNA micromanipulation , 2000 .

[121]  Kai Simons,et al.  Lipid rafts and signal transduction , 2000, Nature Reviews Molecular Cell Biology.

[122]  Daniel J. Müller,et al.  Observing single biomolecules at work with the atomic force microscope , 2000, Nature Structural Biology.

[123]  V. Sandoghdar,et al.  Optical microscopy using a single-molecule light source , 2000, Nature.

[124]  M. Gustafsson Surpassing the lateral resolution limit by a factor of two using structured illumination microscopy , 2000, Journal of microscopy.

[125]  Toshio Yanagida,et al.  Single-molecule imaging of EGFR signalling on the surface of living cells , 2000, Nature Cell Biology.

[126]  H. Güntherodt,et al.  Dynamic force spectroscopy of single DNA molecules. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[127]  Matthias Rief,et al.  Single molecule force spectroscopy by AFM indicates helical structure of poly(ethylene-glycol) in water , 1999 .

[128]  W. Moerner,et al.  Illuminating single molecules in condensed matter. , 1999, Science.

[129]  E. Ikonen,et al.  Functional rafts in cell membranes , 1997, Nature.

[130]  W. Webb,et al.  Constrained diffusion or immobile fraction on cell surfaces: a new interpretation. , 1996, Biophysical journal.

[131]  S. Chu,et al.  Quantitative measurements of force and displacement using an optical trap. , 1996, Biophysical journal.

[132]  S. Hell,et al.  Breaking the diffraction resolution limit by stimulated emission: stimulated-emission-depletion fluorescence microscopy. , 1994, Optics letters.

[133]  J. Skehel,et al.  Binding of influenza virus hemagglutinin to analogs of its cell-surface receptor, sialic acid: analysis by proton nuclear magnetic resonance spectroscopy and X-ray crystallography. , 1994, Biochemistry.

[134]  U. Dürig,et al.  Near‐field optical‐scanning microscopy , 1986 .

[135]  M. Bretscher,et al.  Mammalian plasma membranes , 1975, Nature.

[136]  Hugh Davson,et al.  A contribution to the theory of permeability of thin films , 1935 .

[137]  E. Gorter,et al.  ON BIMOLECULAR LAYERS OF LIPOIDS ON THE CHROMOCYTES OF THE BLOOD , 1925, The Journal of experimental medicine.

[138]  Xue-Bo Yin,et al.  Review on Carbon Dots and Their Applications , 2017 .

[139]  S. Mayor,et al.  Homo-FRET imaging highlights the nanoscale organization of cell surface molecules. , 2015, Methods in molecular biology.

[140]  X. Zhuang,et al.  Monitoring conformational dynamics with single-molecule fluorescence energy transfer: applications in nucleosome remodeling. , 2012, Methods in enzymology.

[141]  Ari Helenius,et al.  Virus entry by endocytosis. , 2010, Annual review of biochemistry.

[142]  Mark M Davis,et al.  TCR and Lat are expressed on separate protein islands on T cell membranes and concatenate during activation , 2010, Nature Immunology.

[143]  A. Aderem,et al.  Mechanisms of phagocytosis in macrophages. , 1999, Annual review of immunology.

[144]  Gerber,et al.  Atomic Force Microscope , 2020, Definitions.

[145]  S. Singer,et al.  The fluid mosaic model of the structure of cell membranes. , 1972, Science.

[146]  Th. Förster Zwischenmolekulare Energiewanderung und Fluoreszenz , 1948 .