visit at McMaster reactor feb 2024

Giovanna Fragneto

Science Director

Research Activities

The focus of my research activities is the structural characterisation and  the study of fluctuations of model biological membranes with the aim of understanding phenomena at cell surfaces. Examples include the interaction of membranes with peptides, proteins, drugs or drug delivery systems. Systems are mainly planar and studied by neutron or x-ray reflectometry. 

  • Structure of natural and model membranes by reflectometry and diffraction: interaction of lipids with biomolecules
  • Deuterated Natural Lipid Extraction for structural characterisation of model membranes (coll.: H. Wacklin-Knecht, K. Batchu, A. Luchini, G. Corucci)
  • Determination of bending modulus and in-plane features of floating bilayers by grazing-incidence synchrotron radiation (coll.:  T. Charitat, J. Daillant & al.)
  • Lipid rafts mimicks structural characterisation (coll.: L. Cantù, V. Rondelli)
  • Lipid Flip-Flop (coll.: Yuri Gerelli, Lionel Porcar, Ursula Perez-Salas)
  • Interaction of nano particles with membranes (coll. Maccarini, Baldelli)
  • Deuterated protein/PEG interactions (coll.: E. Schneck, M. Sferrazza, A. Halperin) 
  • Liquid/liquid interfaces (coll.: E. Scoppola, O. Diat, O. Konovalov, E. Watkins, R. Campbell, P. Gutfreund)
  • Flash-cooling phospholipid bilayers (coll.: M. Weik, J. Zaccai)

Real biological membranes have different components, including lipids, sterols and proteins, which are distributed very heterogeneously, forming domains that are involved in the transmission of signals between the inside and the outside of the cell. Current efforts are devoted to exploring systems, such as natural lipids extracted from cells, to get closer to this complex reality.

Optical, electron, and atomic force microscopies have come a long way in recent decades. However, neutron scattering gives complementary and unique information and is increasingly widely used. One of its more and more frequent applications is the study of the nanoscale structure of model membranes and their interactions with proteins or peptides participating in important cellular functions.

Protein deuteration is becoming a common technique coupled to neutrons to refine details of protein-lipid interactions and protein structure at interfaces: deuteration of other membrane components like lipids and sterols have also made steady progress in recent years. Neutron scattering at small angles has nanometer resolution and, unlike crystallographic techniques, can be used to probe membranes in physiological conditions or in-vivo and follow processes in-situ.

Recently we have shown that it is possible to prepare extracts of true natural yeast membranes and prepare with them reproducible and stable bilayers. This allowed the study of the mechanism of interaction of an antibiotic molecule like amphotericin with natural membranes containing sterol.
Work is in progress to optimize methods to produce bilayers from natural lipid extracts on soft cushions and to separate the different lipid species from the extracts.

A very topical issue in this field is also the development of reliable protocols for reconstitution of membrane proteins into model membranes. Smart measurement setups and data analysis procedures have already allowed the acquisition of precious information on membrane protein function. The coupling of scattering and MD simulations has been recently reviewed.
Interesting developments for the study of liquid-liquid interfaces with neutron reflectometry have been possible recently thanks to the possibility to strike the interface with the neutron beam from both sides of a liquid-liquid interface. For example, planar lipid bilayers were prepared and characterized both in the gel and fluid phases at a fluorocarbon-aqueous solution interface.
Neutron work at the liquid-liquid interface has been limited in the past by the poor transmission of neutrons through liquids, even if deuterated. The universal law of attenuation of radiation passing through matter (Beer-Lambert law) is also valid for neutron transmission. Fluorocarbons transmit neutrons well (larger penetration depth than for hydrocarbons) and are denser than water. This allows the use of bulk liquids with large enough surfaces to illuminate the sample away from the meniscus (for reflectometry measurements samples must be flat to avoid cumbersome procedures of data normalization). Partially negatively charged bilayers from POPC containing 30 mol % POPS were formed from vesicle fusion in the presence of salt from the aqueous side of the interfaces on a positively charged monolayer from 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) and di-stearoylpropyl trimonium chloride (DSTAP) (7:3 mol:mol) created at the fluorocarbon-aqueous solution interface. A bilayer with good coverage was produced from which the distance of the interface varied with salt content. The interest of producing bilayers at a liquid-liquid interface lies in the possibility to have a model fluctuating between fluid media adapted for characterization at the fraction of nanometer level with ease of manipulation and possibility to determine the effect of thermodynamic parameters or interacting biomolecules. The transport across the interface should be easier than when bilayers are adjacent to a solid surface.

This and other interesting developments confirm that in the biology of the future, physics should play a major role. If we fully exploit their potential, neutrons can help unravel the secrets of life.

Selected Publications

Luchini A., Micciulla S., Corucci G., Batchu K.C., Santamaria A., Laux V., Darwish T., Russell R.A., Thépaut M., Bally I., Fieschi F., Fragneto G.* - Lipid bilayer degradation induced by SARS-CoV-2 spike protein as revealed by neutron reflectometry
Scientific Reports 11, 14867-1-14867-11 (2021)
Mukhina T., Gerelli Y., Hemmerle A., Koutsioubas A., Kovalev K., Teulon J.M., Pellequer J.L., Daillant J., Charitat T., Fragneto G.* - Insertion and activation of functional Bacteriorhodopsin in a floating bilayer
Journal of Colloid and Interface Science 597, 370-382 (2021)
Meineke J., Weik M., Zaccaï G., Fragneto G.* - Behavior of hydrated lipid bilayers at cryogenic temperatures
Frontiers in Chemistry 8,  455-1-455-7 (2020)
The Role of Temperature and Lipid Charge on Intake/Uptake of Cationic Gold Nanoparticles into Lipid Bilayers
Lolicato, Fabio; Joly, Loic; Martinez-Seara, Hector; et al.
SMALL 2019, 15 (23) 1805046
Neutron reflectometry from poly (ethylene-glycol) brushes binding anti-PEG antibodies: Evidence of ternary adsorption
Emanuel Schneck, Ida Berts, Avraham Halperin, Jean Daillant, Giovanna Fragneto*
Biomaterials 04/2015; 46. DOI:10.1016/j.biomaterials.2014.12.041
Production and Analysis of Perdeuterated Lipids from Pichia pastoris Cells
de Ghellinck, Alexis; Schaller, Hubert; Laux, Valerie; M. Haertlein; M. Sferrazza; H. Wacklin; J. Johuet; G. Fragneto*
Plos One  Volume: 9  Issue: 4     Article Number: e92999   Published: APR 18 2014
Competition for Space Between a Protein and Lipid Monolayers
Giovanna Fragneto, Stéphane Alexandre, Jean-Marc Valleton, Francis Rondelez
Colloids And Surfaces B: Biointerfaces 103 (2013) 416– 421
Lipid Rearrangement in DSPC/DMPC Bilayers: A Neutron Reflectometry Study
Yuri Gerelli, Lionel Porcar, and Giovanna Fragneto*
Langmuir, 2012, 28 (45), pp 15922–15928
A fluid floating bilayer 
Fragneto G., Charitat T., Graner F., Mecke K., Perino-Gallice L., Bellet-Amalric E. 
Europhys. Lett. Vol. 53 pp. 100-106, 2001
Neutron Reflection Study of Bovine b-Casein Adsorbed on OTS Self-Assembled Monolayers 
Fragneto G., Thomas R. K., Rennie A. R., Penfold J. 
Science, 1995, Vol.267, No.5198, pp.657-660

Career History

since Dec 2022   Science Director at European Spallation Source ERIC (ESS), Lund, SE

Feb 2015 - Nov 2022   Large Scale Structures group leader at the Institut Laue-Langevin (ILL), Grenoble, FR

Sep 2013 - Nov 2022   Responsible for Soft Matter Support and Science group

Jan 2008 - Jan 2015  ILL Senior Fellow - Responsible for promotion and advertising of neutron scattering research activities in the field of soft matter, local contact; Responsible development of the partnership for Soft Condensed Matter (PSCM) with the ESRF. PSCM coordinator from 2008 ESFRI to 2013.

 Jan 2005-Dec 2008   Project Leader: Design, Construction and Installation of the ILL reflectometer FIGARO (budget € 3M - team ~ 30 people). 

Jan 2004-Dec 2007   Co-responsible Reflectometer D17 – Instrumentation maintenance, local contact, soft sample environment, personal research activities in the field of biomembranes. 

Sep 1999-Dec 2003   Responsible Diffractometer D16 - Instrumentation maintenance, local contact, optimisation sample environment, personal research activities in the field of biomembranes. 

Education and Titles

since Jan 2016 Professorship at the Université Grenoble Alpes, Grenoble, FR (Chaire Grands Instruments Européens)

Oct 2012.  Habilitation à Diriger des Recherches (HdR, habilitation for teaching and supervising students) obtained from the École Doctorale de Physique de Grenoble.

May 1997 - May 1999 Post-doc at the ILL with an EC "Training and Mobility Research" grant. Responsible: Dr. Edith Bellet-Amalric. Title: "Interaction of the Peptide Penetratin with a Model Membrane"

Apr 1996 - Apr 1997 Post-doc  at the Laboratoire de Physio-Chimie des Surfaces et Interfaces, Institut Curie, Paris, FR, within the EC contract ERBCHBGCT930477. Responsible: Dr. Francis Rondelez. Title: "Amphiphile monolayers at Fluid Interfaces and Solid Supports"

Nov 1992 - Mar 1996 DPhil work at the Physical and Theoretical Chemistry Laboratory of the University of Oxford, UK. Supervisor: Dr. Robert K. Thomas. Title of DPhil thesis: "Neutron Reflection from Surfactants Adsorbed at Solid/Liquid Interfaces"

Sep 1990 - Jun 1991 Master thesis work (Laurea)  at the Department of Physical Chemistry of the East Anglia University, Norwich, UK, within the EC ERASMUS exchange scheme. Supervisor: Prof. Brian H. Robinson.

Oct 1986 - Oct 1992 Undergraduate and Master studies at the Department of Chemistry of the University of Napoli, I. Title of laurea thesis (110 cum laude):"Properties of Microemulsions: Effects on the Structure of Aerosol-OTBased Water-in-Oil Microemulsions by Variation of Surfactant Counterion"

Languages: Italian (native), English (written, oral), French (written, oral)

Prizes and honors:

since 2011 Member of the editorial board of the European Physical Journal E (EPJE) -  editor-in-chief since 2021

2023 member of ISIS Science Board

2023 recipient of the Darsh Wasan Award from J. Coll. Int. Sci. for “Outstanding achievements in colloids and interface science”

2017-2019 Member of the Scientific Advisory Board of the European Spallation Source (ESS), Lund

2014-2017 Member of “Reflectometry” and “Sample Environment” STAPs at ESS

2012-2016 Member of the Scientific Council of the Research Complex at Harwell, UK

2013-2020 Member of the Partnership for Soft Condensed Matter Steering Committee, ILL

2013 co-editor of the EPJE Topical Issue “Neutron Biological Physics”

2011 co-editor EPJ Plus Focus Point “Advances in Neutron Reflectometry”

2009 Guest Editor Special Issue of EPJE “Biological Physics near Surfaces/Interfaces”

2006 BTM Willis Prize – Prize from the Royal Society of Chemistry and UK Neutron Scattering Group for “Research activities on model membranes”

• Member of Advisory Board/Programme or Organizing Committee of several international conferences, including: ICNS2025, SXNS2024, ECIS 2023, Biophee19, ECNS2019, ICNS10, GEM2017, SXNS11, ISMC2016, ECOSS2016, ECIS2016, ECIS2012, ICNS9, JDN17, SXNS10, ECNS2007, SXNS9, IUCr2005, ICM2003, ICNS2017, ICC2017

• Member of Jury of several PhDs (in Belgium, Denmark, France, Italy, Sweden, UK) and HdR (FR)

• Member of Proposal Review Panels at ILL, HZB, NIST, J-Parc and ANSTO

• Reviewer for EPJE, Scientific Reports, Langmuir, Soft Matter, J. Coll. Int. Sci., ….