Self-Assembly and Structural DNA Nanotechnogy

Several areas of advanced technology require materials with a well defined mesoscale or nanoscale structure, which can only be efficiently obtained via self-assembly of engineered macromolecular or colloidal building blocks. We explore novel strategies for the self-assembly of functional and structural materials, often relying on the unique features of synthetic nucleic acids, utilised as nanoscale Lego bricks or to mediate interactions between particles, substrates and interfaces.
Crystalline Frameworks of Amphiphilic DNA Nanostructures

Introducing C-Stars! These amphiphilic DNA building blocks can robustly self-assemble into crystalline frameworks with extremely high porosity and controllable lattice parameter. 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. Check out our first C-Star paper and stay tuned for upcoming developments...

  • Nano Lett., 17(5), 3276–3281, (2017) [PDF] [LINK]

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!

Biophysics and

Synthetic Biology

We are interested in a various bio-physical problems that we tackle by a combination of experiments, theoretical modelling and computer simulations. We are particularly intrigued by the interaction of biological membranes with other membranes, particles, and proteins, which have deep implications in several biological processes including cell adhesion, tissue dynamics and endocytosis. We often study these processes in artificial biomimetic systems, where experimental parameters can be precisely controlled in order to unravel the underlying physical mechanisms. Our interest in replicating biological processes in vitro goes all the way to the development of artificial cells that display complex life-like behaviours.
Membrane adhesion and the physics of endocytosis

Multivalent interactions between an invader (virus, bacterium) and the membrane of a host cell drive  passive endocytosis, yet the statistical effects of multivalency on the process of membrane wrapping are still to be understood. In recent theoretical and numerical study, performed in collaboration with Dr Bortolo M. Mognetti, we shine light on these phenomena, with focusing on the role played by ligand mobility and excluded volume interactions. Our findings are not only relevant for developing a better understanding of bacterial/viral infection, but may also aid the rational design of intra-cellular nanoparticle probes for nano-medical applications. Check out our preprint!

Protein-membrane interactions

Amyloid protein aggregates are associate to cellular damage in a number of pathologies including type 2 diabetes, Alzheimer's and Parkinson's. Membrane destabilisation by protein aggregates is thought to be a primary cytotoxicity mechanism. In collaboration with Dr Vito Foderà, we study how different types of protein aggregates interact with biomimetic membranes, trying to identify subtle physical alterations that precede large scale membrane disruption. To do so, we employ a non-invasive characterisation technique known as flickering spectroscopy, based on the detection of membrane fluctuations in video-microscopy images. See our recent contribution demonstrating how amyloid and pre-fibrillar aggregates decrease the stiffness of lipid membranes.

Also, check out the recent work lead by  Prof. Pietro Cicuta and Prof. Matthew Turner reporting on a critical improvement of flickering spectroscopy.

© 2018 by Lorenzo Di Michele