From Membrane Binding to Function: Investigating the Importance of Anionic Lipids in Alpha-Synuclein Biology

Alpha-synuclein, a protein that is abundant in the brain, has been linked to several neurodegenerative disorders, including Parkinson’s disease. Lipids are crucial to the normal function of alpha-synuclein, as well as to the development of disease. In my research, I have investigated the initial interaction between alpha-synuclein and model lipid membranes, which involves membrane remodeling activity, with amyloid fibril formation occurring during longer incubation periods. I have examined the impact of various factors, such as the composition of model lipid membranes, protein variants, and the presence of molecules that remain bound to neuronal membranes under physiological conditions, on the outcome of this reaction. Using a combination of methods, including spectroscopy and microscopy, I have studied the interaction between alpha-synuclein and model lipid membranes. The results of these studies provide new insights into the role of lipids in the biology of alpha-synuclein and may contribute to the development of novel therapies for neurodegenerative disorders.

Functionalization of boundaries in active nematics: inclusions and confinement.

Active fluids and their spontaneous flows promise exciting new paths toward efficient transport phenomena and new autonomous materials. However, the fulfillment of this promise pends on finding effective ways to control them. In this regard, an auspicious avenue is the use of inclusions and confinement, which, in its simplest form, has led to the emergence of long-lived coordinated flows. Here we extend these efforts in two different ways: First, we show how combining custom anchoring conditions within nematic colloidal inclusions can lead to an effective self-propulsion. In particular, we show how the steering dynamics of such self-propulsion is intimately linked to the dynamics of a companion -1/2 topological defect. Second, by expanding to 3D channels, we show how confinement can lead to spontaneous helical flows that break chiral symmetry both locally and globally. As such, this work demonstrates the potential of confinement geometry to unravel complex but organized spatiotemporal structures in active liquid crystals, thus showing that they may present a path to functionality.

Single-Molecule Structure and Topology of Kinetoplast DNA Networks

The Kinetoplast DNA (kDNA) is a 2D network of mutually inter-linked DNA minicircles found in Trypanosomes that heavily resembles an “Olympic gel”. Understanding the self-assembly and replication of this structure are not only major open questions in biology but can also inform the design of synthetic topological materials such as polycatenanes, dubbed as “the Holy Grail of Polymer Chemistry” by Nobel laureate Sir Fraser Stoddart.
In this talk I will present the first high-resolution, single-molecule study of kDNA network topology using AFM and steered molecular dynamics simulations. We accurately measure the spatial distribution of DNA in the network and quantify the distribution of valence of the minicircles. Additionally, we use sub-isostatic network theory to characterise the elastic Young modulus and bending stiffness of the network, and discover that they are 10^6 and 10^3 times smaller than the ones in typical 2D materials such as lipid membranes, thus rendering the kDNA the first example of a “ultra-soft” topological gel.
Our findings explain outstanding questions in the biology of kDNA and offer single-molecule insights into the properties of a unique topological material.