Integrin-Functionalised Giant Unilamellar Vesicles via Gel-Assisted Formation: Good Practices and Pitfalls

Giant unilamellar vesicles (GUV) are powerful tools to explore physics and biochemistry of the cell membrane in controlled conditions. For example, GUVs were extensively used to probe cell adhesion, but often using non-physiological linkers, due to the difficulty of incorporating transmembrane adhesion proteins into model membranes. Here we describe a new protocol for making GUVs incorporating the transmembrane protein integrin using gel-assisted swelling. We report an optimised protocol, enumerating the pitfalls encountered and precautions to be taken to maintain the robustness of the protocol. We characterise intermediate steps of small proteoliposome formation and the final formed GUVs. We show that the integrin molecules are successfully incorporated and are functional.

[1]  Cécile Leduc,et al.  Cell stretching is amplified by active actin remodelling to deform and recruit proteins in mechanosensitive structures , 2020, Nature Cell Biology.

[2]  W. Weissenhorn,et al.  The ESCRT protein CHMP2B acts as a diffusion barrier on reconstituted membrane necks , 2019, Journal of Cell Science.

[3]  D. Klenerman,et al.  A cell topography-based mechanism for ligand discrimination by the T cell receptor , 2019, Proceedings of the National Academy of Sciences.

[4]  O. Pierre-Louis,et al.  Adhesion dynamics of confined membranes. , 2018, Soft matter.

[5]  M. Prieto,et al.  Membrane properties of giant polymer and lipid vesicles obtained by electroformation and pva gel-assisted hydration methods , 2017 .

[6]  K. Garcia,et al.  In vitro reconstitution of T cell receptor-mediated segregation of the CD45 phosphatase , 2017, Proceedings of the National Academy of Sciences.

[7]  J. V. Hest,et al.  Evaluation of dextran(ethylene glycol) hydrogel films for giant unilamellar lipid vesicle production and their application for the encapsulation of polymersomes. , 2017, Soft matter.

[8]  U. Seifert,et al.  Membrane fluctuations mediate lateral interaction between cadherin bonds , 2017, Nature Physics.

[9]  Vahid Sandoghdar,et al.  Production of Isolated Giant Unilamellar Vesicles under High Salt Concentrations , 2017, Front. Physiol..

[10]  K. Sengupta,et al.  Measuring shape fluctuations in biological membranes , 2016 .

[11]  U. Seifert,et al.  Measuring fast stochastic displacements of bio-membranes with dynamic optical displacement spectroscopy , 2015, Nature Communications.

[12]  B. Geiger,et al.  Minimal Synthetic Cells to Study Integrin-Mediated Adhesion , 2015, Angewandte Chemie.

[13]  R. Forster,et al.  The lateral diffusion and fibrinogen induced clustering of platelet integrin αIIbβ3 reconstituted into physiologically mimetic GUVs. , 2015, Integrative biology : quantitative biosciences from nano to macro.

[14]  Gerhard Gompper,et al.  Equilibrium physics breakdown reveals the active nature of red blood cell flickering , 2015, Nature Physics.

[15]  M. Davidson,et al.  The cancer glycocalyx mechanically primes integrin-mediated growth and survival , 2014, Nature.

[16]  G. Pabst,et al.  Liposomes, Lipid Bilayers and Model Membranes : From Basic Research to Application , 2014 .

[17]  C. Le Clainche,et al.  Actomyosin-dependent formation of the mechanosensitive talin–vinculin complex reinforces actin anchoring , 2014, Nature Communications.

[18]  Ulrich S. Schwarz,et al.  Physics of adherent cells , 2013, 1309.2817.

[19]  André Schröder,et al.  Gel-assisted formation of giant unilamellar vesicles. , 2013, Biophysical journal.

[20]  Patricia Bassereau,et al.  Detergent-mediated incorporation of transmembrane proteins in giant unilamellar vesicles with controlled physiological contents , 2013, Proceedings of the National Academy of Sciences.

[21]  F. Höök,et al.  Equilibrium-fluctuation-analysis of single liposome binding events reveals how cholesterol and Ca2+ modulate glycosphingolipid trans-interactions , 2013, Scientific Reports.

[22]  P. Westh,et al.  Analysis of the shape fluctuations of reconstituted membranes using GUVs made from lipid extracts of invertebrates , 2013, Biology Open.

[23]  Daniel Choquet,et al.  Integrins β1 and β3 exhibit distinct dynamic nanoscale organizations inside focal adhesions , 2012, Nature Cell Biology.

[24]  Kheya Sengupta,et al.  Giant vesicles as cell models. , 2012, Integrative biology : quantitative biosciences from nano to macro.

[25]  R. Lipowsky,et al.  Vesicles with multiple membrane domains , 2011 .

[26]  Manouk Abkarian,et al.  Continuous droplet interface crossing encapsulation (cDICE) for high throughput monodisperse vesicle design , 2011 .

[27]  A. Faraone,et al.  Thermal fluctuation and elasticity of lipid vesicles interacting with pore-forming peptides. , 2010, Physical review letters.

[28]  Pasquale Stano,et al.  Giant Vesicles: Preparations and Applications , 2010, Chembiochem : a European journal of chemical biology.

[29]  K. Sengupta,et al.  Adhesion of soft membranes controlled by tension and interfacial polymers. , 2010, Physical review letters.

[30]  P. Bassereau,et al.  Integrin reconstituted in GUVs: a biomimetic system to study initial steps of cell spreading. , 2009, Biochimica et biophysica acta.

[31]  Jay T. Groves,et al.  Cluster size regulates protein sorting in the immunological synapse , 2009, Proceedings of the National Academy of Sciences.

[32]  Andrés J. García,et al.  Demonstration of catch bonds between an integrin and its ligand , 2009, The Journal of cell biology.

[33]  R. Merkel,et al.  Diffusion and intermembrane distance: case study of avidin and E-cadherin mediated adhesion. , 2009, Langmuir : the ACS journal of surfaces and colloids.

[34]  E. Sackmann,et al.  Progress in mimetic studies of cell adhesion and the mechanosensing. , 2009, Chemphyschem : a European journal of chemical physics and physical chemistry.

[35]  J. Jara,et al.  Sphingomyelinase-induced domain shape relaxation driven by out-of-equilibrium changes of composition. , 2009, Biophysical journal.

[36]  U. Seifert,et al.  Dynamics of specific vesicle-substrate adhesion: from local events to global dynamics. , 2008, Physical review letters.

[37]  Viola Vogel,et al.  Catch-bond mechanism of force-enhanced adhesion: counterintuitive, elusive, but ... widespread? , 2008, Cell host & microbe.

[38]  T. Pott,et al.  Giant unilamellar vesicle formation under physiologically relevant conditions. , 2008, Chemistry and physics of lipids.

[39]  U. Seifert,et al.  Force-induced growth of adhesion domains is controlled by receptor mobility , 2008, Proceedings of the National Academy of Sciences.

[40]  K. Sengupta,et al.  Modulation of vesicle adhesion and spreading kinetics by hyaluronan cushions. , 2007, Biophysical journal.

[41]  A. Tian,et al.  Flicker spectroscopy of thermal lipid bilayer domain boundary fluctuations. , 2007, Biophysical journal.

[42]  E. Sackmann,et al.  Adhesion of giant vesicles mediated by weak binding of sialyl-LewisX to E-selectin in the presence of repelling poly(ethylene glycol) molecules. , 2007, Langmuir : the ACS journal of surfaces and colloids.

[43]  Watt W. Webb,et al.  Large-scale fluid/fluid phase separation of proteins and lipids in giant plasma membrane vesicles , 2007, Proceedings of the National Academy of Sciences.

[44]  D. Fletcher,et al.  Actin polymerization serves as a membrane domain switch in model lipid bilayers. , 2006, Biophysical journal.

[45]  Benjamin Geiger,et al.  Adhesion-mediated mechanosensitivity: a time to experiment, and a time to theorize. , 2006, Current opinion in cell biology.

[46]  M. Sheetz,et al.  Local force and geometry sensing regulate cell functions , 2006, Nature Reviews Molecular Cell Biology.

[47]  Alexander Roth,et al.  Microviscoelastic moduli of biomimetic cell envelopes. , 2005, Physical review letters.

[48]  P. Bassereau,et al.  Role of curvature and phase transition in lipid sorting and fission of membrane tubules , 2005, The EMBO journal.

[49]  P. Schwille,et al.  SNAREs Prefer Liquid-disordered over “Raft” (Liquid-ordered) Domains When Reconstituted into Giant Unilamellar Vesicles*[boxs] , 2004, Journal of Biological Chemistry.

[50]  Patricia Bassereau,et al.  A new method for the reconstitution of membrane proteins into giant unilamellar vesicles. , 2004, Biophysical journal.

[51]  Mario Corti,et al.  Shape fluctuations of large unilamellar lipid vesicles observed by laser light scattering: influence of the small-scale structure. , 2004, Langmuir : the ACS journal of surfaces and colloids.

[52]  P. Gennes,et al.  Adhesion Induced by Mobile Stickers: A List of Scenarios , 2003 .

[53]  E. Sackmann,et al.  On the organization of self-assembled actin networks in giant vesicles , 2003, The European physical journal. E, Soft matter.

[54]  Owe Orwar,et al.  Artificial cells: Unique insights into exocytosis using liposomes and lipid nanotubes , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[55]  P. Luisi,et al.  The Use of Liposomes for Constructing Cell Models , 2002, Journal of biological physics.

[56]  E. Sackmann,et al.  Polymorphism of cross-linked actin networks in giant vesicles. , 2002, Physical review letters.

[57]  E. Sackmann,et al.  Helfrich repulsion and dynamical phase separation of multicomponent lipid bilayers. , 2002, Physical review letters.

[58]  E. Sackmann,et al.  Kinetics of membrane adhesion mediated by ligand-receptor interaction studied with a biomimetic system. , 2001, Biophysical journal.

[59]  D. Wiersma,et al.  Reconstitution of membrane proteins into giant unilamellar vesicles via peptide-induced fusion. , 2001, Biophysical journal.

[60]  F. MacKintosh,et al.  Buckling of actin-coated membranes under application of a local force. , 2001, Physical review letters.

[61]  E. Sackmann,et al.  Measuring Ligand−Receptor Unbinding Forces with Magnetic Beads: Molecular Leverage† , 2000 .

[62]  J. Engel,et al.  Integrin alphaIIb beta3 reconstituted into lipid bilayers is nonclustered in its activated state but clusters after fibrinogen binding. , 1997, Biochemistry.

[63]  M. Ginsberg,et al.  Reconstructing integrin activation in vitro. , 2013, Methods in molecular biology.

[64]  K. Sengupta,et al.  Inferring spatial organization of bonds within adhesion clusters by exploiting fluctuations of soft interfaces , 2010 .

[65]  B. Geiger,et al.  Environmental sensing through focal adhesions , 2009, Nature Reviews Molecular Cell Biology.

[66]  S. Valenzuela Liposome Techniques for Synthesis of Biomimetic Lipid Membranes , 2007 .

[67]  Bin Hu Vesicle Adhesion via Interaction of Integrin alphaIIb betha3 and Cyclic-RGD-Lipopeptide , 2001 .

[68]  E. Evans,et al.  Giant vesicle bilayers composed of mixtures of lipids, cholesterol and polypeptides. Thermomechanical and (mutual) adherence properties. , 1986, Faraday discussions of the Chemical Society.