RICO Felix

• Associate Professor – Maître de conférences at Aix-Marseille Université, Inserm, DyNaMo

• felix.rico@inserm.fr, @felix_rico

• Tel. +33 (0)4 91 82 87 78 // Fax +33 (0)4 91 82 87 01

• ORCID: 0000-0002-7757-8340

• ResearcherID: K-6505-2012

• Google Scholar

• HAL deposit @ Aix-Marseille University

• Mini-CV @Aviesan

Funding

• European Research Council (ERC) Proof of Concept, openFMLab (PI: Rico)

• ANR PRC XXL (PI: Mauro Modesti)

• ANR/NSF BioHETER (PI: Rico)

• European Research Council (ERC) Consolidator Award, MechaDynA (PI: Rico)

• Human Frontier Science Program (HFSP), with M. Sotomayor (Ohio State University, OH, USA), V. Lynch (University of Chicago, IL, USA) and F. Rico (Aix Marseille Univ, Inserm, CNRS)

• H2020-MSCA-ITN Phys2BioMed (co-PI: Rico)

• H2020-MSCA-Cofund Doc2AMU (PhD fellowship, Rico)

• MSCA-IF-2019 BiCiCle Grant agreement ID: 895819 (PI: Rico)

Research – Molecular to cellular mechanics

Mechanical forces are developed within the cell during breathing, muscle contraction or cell migration. The response to mechanical force of cells and subcellular elements, such as the cytoskeleton and adhesion complexes, is thus important to understand their biological role. Our research involves the development and application of advanced atomic force microscopy (AFM and high-speed AFM) to probe the mechanical properties of single molecules and living cells. It is divided in three main axes that interlace and interact with each other.

Funding for this research is provided by ERC, HFSP, PACA region and ANR  (see Funding)

High-speed force spectroscopy (HS-FS) on single molecules

• Bridging the gap between experiments and simulations  (Rico et al. 2013).

• Protein unfolding (Rico et al. 2013; Takahashi et al. 2018; Sumbul et al. 2018).

• Receptor/ligand interactions (Rico et al. 2019).

The development of high-speed atomic force microscopy (HS-AFM) by Prof. Toshio Ando (Kanazawa University, Japan) enabled the visualization of biomolecules at work by allowing the acquisition of AFM movies in the microsecond time scale. My research is primarily focused on the use of HS-AFM to perform force spectroscopy measurements on single biomolecules at high velocities with microsecond time resolution. We now use HS-AFM to perform force spectroscopy measurements on single biomolecules at high velocities with microsecond time resolution. We have recently adapted the HS-AFM system to allow force spectroscopy measurements at the speed of molecular dynamics (MD) simulations (Rico et al. 2013). We unfolded titin immunoglobulin domains at speeds up to ~4 mm/s. Experimental unfolding forces compared well with in silico experiments on the same titin domain. We are now measuring the unbinding forces of the streptavidin-biotin bond to compare them with simulations at the same pulling velocities. The final goal is to apply HS-FS to probe the interaction of adhesion molecules.

Cell mechanics

• High-frequency cell microrheology (Rigato et al. 2017)

• Mechanical mapping of patterned cells (Rigato et al. 2015)

The mechanical properties of living cells are crucial for biological function. We apply different methods based on AFM combined with other techniques to probe the mechanics of cells under various conditions. For example, we use PeakForce mechanical mapping and conventional force spectroscopy to determine the mechanical properties of lens cells and cells grown on micropatterns (Hozic et al. 2012; Rigato et al. 2015). We have recently adapted HS-AFM to carry out high frequency microrheology on living cells (Rigato et al. 2017).

Mechanics and adhesion of membrane proteins

• Mechanical mapping of native membranes, lipid bilayers (Rico et al. 2011; Picas et al. 2012; Rico et al. 2013)

• Dynamic force spectroscopy on adhesion molecules (Rico et al. 2011)

The capacity of proteins to carry out different functions is related to their ability to undergo conformation changes, which depends on the flexibility of protein structures. We applied force-based imaging modes (force mapping, PeakForce) to map quantitatively the flexibility of individual membrane proteins in their native, folded state at unprecedented submolecular resolution. Our results allow us to correlate protein flexibility with crystal structure. We also applied PeakForce to determine the mechanical differences of lipid phases. (Rico et al. 2011; Picas et al. 2012; Rico et al. 2013).

I am also interested on receptor/ligand interactions and, in particular, on adhesion molecules (Rico et al. 2010). We have used dynamic force spectroscopy to determine the adhesion capacity of connexins, membrane proteins that form gap junctions (Rico et al. 2011), and leukocyte adhesion molecules (Rico et al. 2010).