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DNA Nanodevices to Probe and Program Membrane Organization, Dynamics, and Applications

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Abstract

Continuous, dynamic, and controlled membrane remodeling creates flow of information and materials across membranes to sustain life in all biological systems. Multiple nanoscale phenomena of membranes regulate mesoscale processes in cells, which in turn control macro-scale processes in living organisms. Understanding the molecular mechanisms that cells use for membrane homeostasis, i.e., to generate, maintain, and deform the membrane structures has therefore been the mammoth’s task in biology. Using the principles of DNA nanotechnology, researchers can now precisely recapitulate the functional interactions of the biomolecules that can now probe, program, and re-program membrane remodeling and associated phenomena. The molecular mechanisms for membrane dynamics developing in vitro conditions in which the membrane modulating components are precisely organized and modulated by DNA nanoscaffolds are adding new chapters in the field of DNA nanotechnology. In this review, we discuss DNA nanodevices-based membrane remodeling and trafficking machineries and their applications in biological systems.

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References

  • Antonny B et al (2016) Membrane fission by dynamin: what we know and what we need to know. EMBO J 35:2270–2284

    CAS  PubMed  PubMed Central  Google Scholar 

  • Bagheri Y, Shafiei F, Chedid S, Zhao B, You M (2019) Lipid-DNA conjugates for cell membrane modification, analysis, and regulation. Supramol Chem 31:532–544

    CAS  Google Scholar 

  • Bao H et al (2018) Dynamics and number of trans -SNARE complexes determine nascent fusion pore properties. Nature 554:260–263

    CAS  PubMed  PubMed Central  Google Scholar 

  • Baumann KN et al (2020) Coating and stabilization of liposomes by clathrin-inspired DNA self-assembly. ACS Nano 14:2316–2323

    CAS  PubMed  PubMed Central  Google Scholar 

  • Beales PA, Vanderlick TK (2007) Specific binding of different vesicle populations by the hybridization of membrane-anchored DNA. J Phys Chem A 111:12372–12380

    CAS  PubMed  Google Scholar 

  • Beater S, Raab M, Tinnefeld P (2014) Chapter 24—toward quantitative fluorescence microscopy with DNA origami nanorulers. In: Waters JC, Wittman T (eds) Methods in cell biology, vol 123. Academic Press, Cambridge, pp 449–466

    Google Scholar 

  • Bhatia D, Sharma S, Krishnan Y (2011) Synthetic, biofunctional nucleic acid-based molecular devices. Curr Opin Biotechnol 22:475–484

    CAS  PubMed  Google Scholar 

  • Bhatia D, Chakraborty S, Krishnan Y (2012) Designer DNA give RNAi more spine. Nat Nanotechnol 7:344–346

    CAS  PubMed  Google Scholar 

  • Bhatia D et al (2016) Quantum dot-loaded monofunctionalized DNA icosahedra for single-particle tracking of endocytic pathways. Nat Nanotechnol 11:1112–1119

    CAS  PubMed  PubMed Central  Google Scholar 

  • Bian X, Zhang Z, Xiong Q, De Camilli P, Lin C (2019) A programmable DNA-origami platform for studying lipid transfer between bilayers. Nat Chem Biol 15:830–837

    CAS  PubMed  PubMed Central  Google Scholar 

  • Bissig C, Gruenberg J (2013) Lipid sorting and multivesicular endosome biogenesis. Cold Spring Harb Perspect Biol 5:a016816

    PubMed  PubMed Central  Google Scholar 

  • Bombelli FB et al (2009) Closed nanoconstructs assembled by step-by-step ss-DNA coupling assisted by phospholipid membranes. Soft Matter 5:1639–1645

    Google Scholar 

  • Burns JR, Stulz E, Howorka S (2013) Self-assembled DNA nanopores that span lipid bilayers. Nano Lett 13:2351–2356

    CAS  PubMed  Google Scholar 

  • Burns JR, Seifert A, Fertig N, Howorka S (2016) A biomimetic DNA-based channel for the ligand-controlled transport of charged molecular cargo across a biological membrane. Nat Nanotechnol 11:152–156

    CAS  PubMed  Google Scholar 

  • Campsteijn C, Vietri M, Stenmark H (2016) Novel ESCRT functions in cell biology: spiraling out of control? Curr Opin Cell Biol 41:1–8

    CAS  PubMed  Google Scholar 

  • Chan Y-HM, van Lengerich B, Boxer SG (2009) Effects of linker sequences on vesicle fusion mediated by lipid-anchored DNA oligonucleotides. PNAS 106:979–984

    CAS  PubMed  PubMed Central  Google Scholar 

  • Cournia Z et al (2015) Membrane protein structure, function, and dynamics: a perspective from experiments and theory. J Membr Biol 248:611–640

    CAS  PubMed  PubMed Central  Google Scholar 

  • Czogalla A et al (2015) Amphipathic DNA origami nanoparticles to scaffold and deform lipid membrane vesicles. Angew Chem Int Ed 54:6501–6505

    CAS  Google Scholar 

  • Czogalla A, Franquelim HG, Schwille P (2016a) DNA nanostructures on membranes as tools for synthetic biology. Biophys J 110:1698–1707

    CAS  PubMed  PubMed Central  Google Scholar 

  • Czogalla A, Franquelim HG, Schwille P (2016b) DNA nanostructures on membranes as tools for synthetic biology. Biophys J 110:1698–1707

    CAS  PubMed  PubMed Central  Google Scholar 

  • Dave N, Liu J (2011) Programmable assembly of DNA-functionalized liposomes by DNA. ACS Nano 5:1304–1312

    CAS  PubMed  Google Scholar 

  • Dietz H, Douglas SM, Shih WM (2009) Folding DNA into twisted and curved nanoscale shapes. Science 325:725–730

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ding H et al (2018) DNA nanostructure-programmed like-charge attraction at the cell-membrane interface. ACS Cent Sci 4:1344–1351

    CAS  PubMed  PubMed Central  Google Scholar 

  • Dong Y et al (2018) Folding DNA into a lipid-conjugated nanobarrel for controlled reconstitution of membrane proteins. Angew Chem Int Ed 57:2072–2076

    CAS  Google Scholar 

  • Douglas SM, Chou JJ, Shih WM (2007) DNA-nanotube-induced alignment of membrane proteins for NMR structure determination. Proc Natl Acad Sci 104:6644–6648

    CAS  PubMed  PubMed Central  Google Scholar 

  • Dutta PK et al (2018) Programmable multivalent DNA-origami tension probes for reporting cellular traction forces. Nano Lett 18:4803–4811

    CAS  PubMed  PubMed Central  Google Scholar 

  • Franquelim HG, Khmelinskaia A, Sobczak J-P, Dietz H, Schwille P (2018) Membrane sculpting by curved DNA origami scaffolds. Nature Communications 9:811

    PubMed  PubMed Central  Google Scholar 

  • Garcia-Parajo MF, Cambi A, Torreno-Pina JA, Thompson N, Jacobson K (2014) Nanoclustering as a dominant feature of plasma membrane organization. J Cell Sci 127:4995–5005

    PubMed  PubMed Central  Google Scholar 

  • Giancotti FG, Ruoslahti E (1999) Integrin signaling. Science 285:1028–1033

    CAS  PubMed  Google Scholar 

  • Göpfrich K et al (2015) DNA-tile structures induce ionic currents through lipid membranes. Nano Lett 15:3134–3138

    PubMed  Google Scholar 

  • Grome MW, Zhang Z, Pincet F, Lin C (2018) Vesicle tubulation with self-assembling DNA nanosprings. Angew Chem Int Ed 57:5330–5334

    CAS  Google Scholar 

  • Groves JT (2007) Bending mechanics and molecular organization in biological membranes. Annu Rev Phys Chem 58:697–717

    CAS  PubMed  Google Scholar 

  • Heinrich MC et al (2010) Quantifying membrane curvature generation of drosophila amphiphysin N-BAR domains. J Phys Chem Lett 1:3401–3406

    CAS  PubMed  PubMed Central  Google Scholar 

  • Howorka S (2016) Changing of the guard. Science 352:890–891

    CAS  PubMed  Google Scholar 

  • Iric K et al (2018) DNA-encircled lipid bilayers. Nanoscale 10:18463–18467

    CAS  PubMed  Google Scholar 

  • Jakobsen U, Simonsen AC, Vogel S (2008) DNA-controlled assembly of soft nanoparticles. J Am Chem Soc 130:10462–10463

    CAS  PubMed  Google Scholar 

  • Jentsch TJ, Hübner CA, Fuhrmann JC (2004) Ion channels: function unravelled by dysfunction. Nat Cell Biol 6:1039–1047

    CAS  PubMed  Google Scholar 

  • Johannes L, Parton RG, Bassereau P, Mayor S (2015) Building endocytic pits without clathrin. Nat Rev Mol Cell Biol 16:311–321

    CAS  PubMed  Google Scholar 

  • Johnson-Buck A, Jiang S, Yan H, Walter NG (2014) DNA–cholesterol barges as programmable membrane-exploring agents. ACS Nano 8:5641–5649

    CAS  PubMed  Google Scholar 

  • Journot CMA, Ramakrishna V, Wallace MI, Turberfield AJ (2019) Modifying membrane morphology and interactions with DNA origami clathrin-mimic networks. ACS Nano 13:9973–9979

    CAS  PubMed  PubMed Central  Google Scholar 

  • Jovic M, Sharma M, Rahajeng J, Caplan S (2010) The early endosome: a busy sorting station for proteins at the crossroads. Histol Histopathol 25:99–112

    CAS  PubMed  PubMed Central  Google Scholar 

  • Jungmann R et al (2014) Multiplexed 3D cellular super-resolution imaging with DNA-PAINT and Exchange-PAINT. Nat Methods 11:313–318

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ke Y, Ong LL, Shih WM, Yin P (2012) Three-dimensional structures self-assembled from DNA bricks. Science 338:1177–1183

    CAS  PubMed  Google Scholar 

  • Kholodenko BN (2006) Cell-signalling dynamics in time and space. Nat Rev Mol Cell Biol 7:165–176

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kocabey S et al (2015) Membrane-assisted growth of DNA origami nanostructure arrays. ACS Nano 9:3530–3539

    CAS  PubMed  PubMed Central  Google Scholar 

  • Krishnan Y, Simmel FC (2011) Nucleic acid based molecular devices. Angew Chem Int Ed 50:3124–3156

    CAS  Google Scholar 

  • Langecker M et al (2012) Synthetic lipid membrane channels formed by designed DNA nanostructures. Science 338:932–936

    CAS  PubMed  PubMed Central  Google Scholar 

  • Liu AP, Fletcher DA (2009) Biology under construction: in vitro reconstitution of cellular function. Nat Rev Mol Cell Biol 10:644–650

    CAS  PubMed  PubMed Central  Google Scholar 

  • Liu X, Lieberman J (2020) Knocking ’em dead: pore-forming proteins in immune defense. Annu Rev Immunol 38:455–485

    CAS  PubMed  PubMed Central  Google Scholar 

  • Maingi V et al (2017) Stability and dynamics of membrane-spanning DNA nanopores. Nat Commun 8:14784

    CAS  PubMed  PubMed Central  Google Scholar 

  • McCluskey JB, Clark DS, Glover DJ (2020) Functional applications of nucleic acid-protein hybrid nanostructures. Trends Biotechnol 38:976

    PubMed  Google Scholar 

  • McMahon HT, Boucrot E (2015) Membrane curvature at a glance. J Cell Sci 128:1065–1070

    CAS  PubMed  PubMed Central  Google Scholar 

  • Mim C, Unger VM (2012) Membrane curvature and its generation by BAR proteins. Trends Biochem Sci 37:526–533

    CAS  PubMed  PubMed Central  Google Scholar 

  • Modi S, Bhatia D, Simmel FC, Krishnan Y (2010) Structural DNA nanotechnology: from bases to bricks, from structure to function. J Phys Chem Lett 1:1994–2005

    CAS  Google Scholar 

  • Modi S, Nizak C, Surana S, Halder S, Krishnan Y (2013) Two DNA nanomachines map pH changes along intersecting endocytic pathways inside the same cell. Nat Nanotechnol 8:459–467

    CAS  PubMed  Google Scholar 

  • Morlot S, Roux A (2013) Mechanics of dynamin-mediated membrane fission. Annu Rev Biophys 42:629–649

    CAS  PubMed  PubMed Central  Google Scholar 

  • Nickels PC et al (2016) Molecular force spectroscopy with a DNA origami–based nanoscopic force clamp. Science 354:305–307

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ohmann A et al (2019) Controlling aggregation of cholesterol-modified DNA nanostructures. Nucleic Acids Res 47:11441–11451

    CAS  PubMed  PubMed Central  Google Scholar 

  • Park SH et al (2005) Programmable DNA self-assemblies for nanoscale organization of ligands and proteins. Nano Lett 5:729–733

    CAS  PubMed  Google Scholar 

  • Peng P et al (2020) Extracellular ion-responsive logic sensors utilizing DNA dimeric nanoassemblies on cell surface and application to boosting AS1411 internalization. Anal Chem 92:9273–9280

    CAS  PubMed  Google Scholar 

  • Perrault SD, Shih WM (2014) Virus-inspired membrane encapsulation of DNA nanostructures to achieve in vivo stability. ACS Nano 8:5132–5140

    CAS  PubMed  PubMed Central  Google Scholar 

  • Peruzzi JA, Jacobs ML, Vu TQ, Wang KS, Kamat NP (2019) Barcoding biological reactions with DNA-functionalized vesicles. Angew Chem Int Ed 58:18683–18690

    CAS  Google Scholar 

  • Raiborg C, Stenmark H (2009) The ESCRT machinery in endosomal sorting of ubiquitylated membrane proteins. Nature 458:445–452

    CAS  PubMed  Google Scholar 

  • Rothemund P (2006) Folding DNA to create nanoscale shapes and patterns. Nature 440:297–302

    CAS  PubMed  Google Scholar 

  • Rothman JE (1994) Mechanisms of intracellular protein transport. Nature 372:55–63

    CAS  PubMed  Google Scholar 

  • Roux A et al (2010) Membrane curvature controls dynamin polymerization. PNAS 107:4141–4146

    CAS  PubMed  PubMed Central  Google Scholar 

  • Royle SJ (2006) The cellular functions of clathrin. Cell Mol Life Sci 63:1823–1832

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ryu J-K, Jahn R, Yoon T-Y (2016) Review: Progresses in understanding N-ethylmaleimide sensitive factor (NSF) mediated disassembly of SNARE complexes. Biopolymers 105:518–531

    CAS  PubMed  Google Scholar 

  • Sarangi NK, Ayappa KG, Visweswariah SS, Basu JK (2016) Nanoscale dynamics of phospholipids reveals an optimal assembly mechanism of pore-forming proteins in bilayer membranes. Phys Chem Chem Phys 18:29935–29945

    CAS  PubMed  Google Scholar 

  • Schmidt O, Teis D (2012) The ESCRT machinery. Curr Biol 22:R116–R120

    CAS  PubMed  PubMed Central  Google Scholar 

  • Schmied JJ et al (2014) DNA origami–based standards for quantitative fluorescence microscopy. Nat Protoc 9:1367–1391

    CAS  PubMed  Google Scholar 

  • Schuh AL, Audhya A (2014) The ESCRT machinery: from the plasma membrane to endosomes and back again. Crit Rev Biochem Mol Biol 49:242–261

    CAS  PubMed  PubMed Central  Google Scholar 

  • Seifert A et al (2015) Bilayer-spanning DNA nanopores with voltage-switching between open and closed state. ACS Nano 9:1117–1126

    CAS  PubMed  Google Scholar 

  • Sharonov A, Hochstrasser RM (2006) Wide-field subdiffraction imaging by accumulated binding of diffusing probes. PNAS 103:18911–18916

    CAS  PubMed  PubMed Central  Google Scholar 

  • Simunovic M, Voth GA, Callan-Jones A, Bassereau P (2015) When physics takes over: BAR proteins and membrane curvature. Trends Cell Biol 25:780–792

    CAS  PubMed  PubMed Central  Google Scholar 

  • Singh M, Jadhav HR, Bhatt T (2017) Dynamin functions and ligands: classical mechanisms behind. Mol Pharmacol 91:123–134

    CAS  PubMed  Google Scholar 

  • Stanishneva-Konovalova TB, Derkacheva NI, Polevova SV, Sokolova OS (2016) The role of BAR domain proteins in the regulation of membrane dynamics. Acta Nat 8:60–69

    CAS  Google Scholar 

  • Steinhauer C, Jungmann R, Sobey TL, Simmel FC, Tinnefeld P (2009) DNA Origami as a nanoscopic ruler for super-resolution microscopy. Angew Chem Int Ed 48:8870–8873

    CAS  Google Scholar 

  • Stephanopoulos N (2019) Peptide-oligonucleotide hybrid molecules for bioactive nanomaterials. Bioconj Chem 30:1915–1922

    CAS  Google Scholar 

  • Suzuki Y, Endo M, Sugiyama H (2015) Mimicking membrane-related biological events by DNA origami nanotechnology. ACS Nano 9:3418–3420

    CAS  PubMed  Google Scholar 

  • Tam DY, Lo PK (2015) Multifunctional DNA nanomaterials for biomedical applications. J Nanomater 2015:e765492

    Google Scholar 

  • Taylor MJ, Husain K, Gartner ZJ, Mayor S, Vale RD (2017) A DNA-based T cell receptor reveals a role for receptor clustering in ligand discrimination. Cell 169:108-119.e20

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ungermann C, Langosch D (2005) Functions of SNAREs in intracellular membrane fusion and lipid bilayer mixing. J Cell Sci 118:3819–3828

    CAS  PubMed  Google Scholar 

  • Van Meer G, Voelker DR, Feigenson GW (2008) Membrane lipids: where they are and how they behave. Nat Rev Mol Cell Biol 9:112–124

    PubMed  PubMed Central  Google Scholar 

  • Veneziano R et al (2020) Role of nanoscale antigen organization on B-cell activation probed using DNA origami. Nat Nanotechnol. https://doi.org/10.1038/s41565-020-0719-0

    Article  PubMed  PubMed Central  Google Scholar 

  • Wang S, Bellen HJ (2015) The retromer complex in development and disease. Development 142:2392–2396

    CAS  PubMed  PubMed Central  Google Scholar 

  • Wang P et al (2018) Visualization of the cellular uptake and trafficking of DNA origami nanostructures in cancer cells. J Am Chem Soc 140:2478–2484

    CAS  PubMed  PubMed Central  Google Scholar 

  • Xu W et al (2016) A programmable DNA origami platform to organize SNAREs for membrane fusion. J Am Chem Soc 138:4439–4447

    CAS  PubMed  PubMed Central  Google Scholar 

  • Yang Y et al (2016) Self-assembly of size-controlled liposomes on DNA nanotemplates. Nat Chem 8:476–483

    CAS  PubMed  PubMed Central  Google Scholar 

  • Yin P et al (2008) Programming DNA tube circumferences. Science 321:824–826

    CAS  PubMed  Google Scholar 

  • Yoshina-Ishii C, Boxer SG (2003) Arrays of mobile tethered vesicles on supported lipid bilayers. J Am Chem Soc 125:3696–3697

    CAS  PubMed  Google Scholar 

  • Zatsepin TS, Oretskaya TS (2004) Synthesis and applications of oligonucleotide carbohydrate conjugates. Chem Biodivers 1:1401–1417

    CAS  PubMed  Google Scholar 

  • Zhang Z, Chapman ER (2020) Programmable nanodisc patterning by DNA origami. Nano Lett 20:6032–6037

    CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang Z et al (2014) DNA-scaffolded multivalent ligands to modulate cell function. ChemBioChem 15:1268–1273

    CAS  PubMed  Google Scholar 

  • Zhang Z, Yang Y, Pincet F, Llaguno M, Lin C (2017) Placing and shaping liposomes with reconfigurable DNA nanocages. Nat Chem 9:653–659

    CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang P et al (2020) Capturing transient antibody conformations with DNA origami epitopes. Nat Commun 11:3114

    CAS  PubMed  PubMed Central  Google Scholar 

  • Zhao Z et al (2018) DNA-corralled nanodiscs for the structural and functional characterization of membrane proteins and viral entry. J Am Chem Soc 140:10639–10643

    CAS  PubMed  PubMed Central  Google Scholar 

  • Zhu C, Das SL, Baumgart T (2012) Nonlinear sorting, curvature generation, and crowding of endophilin N-BAR on tubular membranes. Biophys J 102:1837–1845

    CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We thank all the members of DB lab for critical inputs over this review. DB thanks IITGN for start-up grant and SERB-DST for Ramanujan fellowship and BRNS-BARC for research grant. AR, VM, and SK thank MHRD for research fellowships.

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  1. Anjali Rajwar, Vinod Morya, and Sumit Kharbanda have contributed equally to this work.

Authors and Affiliations

  1. Biological Engineering, Indian Institute of Technology Gandhinagar, Palaj, Gandhinagar, Gujarat, 382355, India

    Anjali Rajwar, Vinod Morya, Sumit Kharbanda & Dhiraj Bhatia

  2. Centre for Biomedical Engineering, Indian Institute of Technology Gandhinagar, Palaj, Gandhinagar, Gujarat, 382355, India

    Dhiraj Bhatia

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  1. Anjali Rajwar
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Rajwar, A., Morya, V., Kharbanda, S. et al. DNA Nanodevices to Probe and Program Membrane Organization, Dynamics, and Applications. J Membrane Biol 253, 577–587 (2020). https://doi.org/10.1007/s00232-020-00154-x

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