Research Highlights
Welcome to our research page. Below are a few highlights on the groups's work on various topics, spanning from soft matter and biophysics, to artificial cells, materials and super-resolution microscopy. In almost all our work DNA nanotechnology appears in one form or the other. The idea behind this amazing discipline is that of using DNA as a building material rather than for its biological meaning, which is made possible thanks to the the unique physical and chemical properties of nucleic acids, including the ability of forming highly selective base-pairing bonds. We try to keep this page reasonably updated, but refer to the publications section and our Twitter profile (@DiMicheleLab1) for the latest developments!
Frameworks of Amphiphilic DNA Nanostructures
Introducing C-Stars! These amphiphilic DNA building blocks can robustly self-assemble into crystalline frameworks with high porosity and controllable lattice parameter, but can also form amorphous hydrogels with programmable properties. C-Stars are "simple" star-shaped DNA junctions in which each "arm" terminates in a cholesterol molecule. C-Stars frameworks are sustained by a combination hydrophobic interactions and Watson-Crick base pairing, bringing together the robustness of amphiphilic self-assembly and the structural control and potential functionalities of DNA naonstructures. We can make C-Star aggregates form or disassemble when exposed to various stimuli, controllably capture and release molecular cargoes, and even form a sticky network that traps bacteria. Here are some of our papers on C-Stars and related systems:
Multivalent Interactions and Self-Assembly
Multivalent interactions between mesoscopic objects, mediated by a large number of surface anchored molecular linkers, are ubiquitous in biology and a powerful tool for driving the self-assembly of advanced materials. Oftentimes, DNA linkers are utilised to establish multivalent interactions, the physics of which is influenced by a variety of statistical effects that can be exploited to control the equilibrium and kinetic features of the resulting self-assembled materials.
These effects become particularly rich when the molecular linkers can freely diffuse, as in DNA-functionalised liposomes, which we have studied extensively by combining a variety of experimental methods, theory and molecular simulations (coll. Dr Bortolo M. Mognetti, Prof. Pietro Cicuta). Browse our papers on the topic:
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Nature. Comm., 6:5948, (2015) [LINK]
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PCCP, 15(9), 3115-3129, (2015) [LINK]
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ACS Nano, 10(2), 2392-2398, (2016) [LINK]
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J. Chem. Phys., 144(16), 161104, (2016) [LINK]
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Soft Matter, 12(37), 7804-7817 (2016) [LINK]
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Langmuir, 33(5), 1139-1146 (2017) [LINK]
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Langmuir, 35(6), 2002-2012, (2019) [LINK]
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Rep. Prog. Phys., 82, 116601, (2019) [LINK]
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Nanoscale, 12, 18616-18620, (2020) [LINK]
Bottom-up Synthetic Biology and Artificial Cells
The idea of bottom-up synthetic biology is that of constructing life-like systems from first principles, starting from elementary molecular components. Often these systems take the form of artificial cells, which are micro-robots designed to replicate some of the functionalities normally associated to biological cells, but without being actually alive. These functionalities include energy harvesting and conversion, motion, adaptation and communication, just to give some examples. One can use almost any material to construct artificial cells, from lipids, to polymers, proteins and even colloids or nanoparticles. Our approach instead relies on the tools of DNA nanotech, as they enable the rational design of biomimetic nano-devices that can serve as structural elements and/or functional agents in artificial cells. This area of research is funded by our ERC Starting Grant NANOCELL. Here are some relevant papers:
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Bioconjugate Chem., 30, 1850-1859, (2019) [LINK]
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Nano Lett., 21, 2800–2808, (2021) [LINK]
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J. Am. Chem. Soc. , doi.org/10.1021/jacs.1c065958 (2021) [LINK]
Membrane Biophysics
Lipid membranes are of paramount important in biology, as they regulate several functions of cells and tissues, such as transport, motility, tissue formation and signalling. We are interested in developing a quantitative understanding on the physical principles that underpin emerging phenomena involving lipid bilayers. Examples of problems that we have investigated include thermophoretic phenomena in lipid bilayers and bilayer domains, cation-mediated interaction between membranes and nucleic acids, membrane-protein interactions and passive endocytosis. All of this work has been done in collaboration with many colleagues (Dr B.M. Mognetti, Prof. P. Cicuta, Prof. U. Keyser, Prof. A. Aksimentiev, Prof. V. Fodera and others). Here are some papers to look at for more details:
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Proc. Natl. Acad. Sci. USA, 114(5) 846-851 (2017) [LINK]
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Nature Comm., 8:15351 (2017) [LINK]
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Soft Matter, 13, 3480-3483, (2017) [LINK]
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Phys. Chem. Chem. Phys., 19, 27930-27934, (2017) [LINK]
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Phys. Rev. E, 98, 03240, (2018) [LINK]
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J. Am. Chem. Soc., 143, 7358-7367, (2021) [LINK]
Super-Resolution Optical Microscopy with DNA-PAINT
Optical microscopy is a key technique for biological investigation, because it allows one to examine delicate (even live!) samples in their native state. Unfortunately, however, its resolution is limited by the physics of diffraction, so one cannot distinguish features much smaller than the wavelength of the light used to image. Except that this is no longer true - thanks to super resolution optical techniques! These allow one to beat the diffraction limit and image with resolution down to a few nanometers, which is the key length-scales for several biological processes. One of such techniques is DNA-PAINT, that utilises the controlled binding and unbinding of fluorescent DNA probes to labelled targets to reconstruct super-resolved images. In close collaboration with the super resolution lab of Prof. C. Soeller, we are engaged with developing new DNA nanosystems that can improve on the original idea of DNA-PAINT resulting in e.g. better signal-to-noise ratio and the ability to selectively image protein pairs. Here are some of our contributions:
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Cell Reports, 22(2), 557-567, (2018) [LINK]
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Nano Research, 12, 6141–6154, (2018) [LINK]
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J. Am. Chem. Soc., 142, 12069-12078, (2020) [LINK]
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Nature Comm., 12:501, (2021) [LINK]