Dr. Felix 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.
High-speed force spectroscopy (HS-FS) on single molecules
- Bridge 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.
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.
- 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. in revision).
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).
Most of our publications are freely available from the HAL deposit @ Aix-Marseille University.
- F Sumbul, A Marchesi, F Rico*. History, Rare And Multiple Events Of Mechanical Unfolding Of Repeat Proteins. J Chem Phys, 148(12), 123335 2018
- Takahashi¶, F Rico¶, C Chipot , and S Scheuring. α-Helix Unwinding as Force Buffer in Spectrins. ACS Nano, (in press) (2018). DOI: 10.1021/acsnano.7b08973
- Even C, Abramovici G, Delort F, Rigato AF, Bailleux V, de Sousa Moreira A, P. Vicart, F. Rico, S. Batonnet-Pichon and F. Briki, Mutation in the Core Structure of Desmin Intermediate Filaments Affects Myoblast Elasticity. Biophysical Journal, 113(3): 627-636.
- Schillers, H.; Rianna, C.; Schäpe, J.; Luque, T.; Doschke, H.; Wälte, M.; Uriarte, J.J.; Campillo, N.; Georgios P. A.; Michanetzis, J.; Bobrowska, A.D.; Herruzo, E.T.; Bovio, S.; Parot, P.; Galluzzi, M.; Podestà, A.; Puricelli, A.; Scheuring, S.; Missirlis, Y.; Garcia, R.; Odorico, M.; Teulon, J-M.; Lafont, F.; Lekka, M.; Rico, F.; Rigato, A.; Pellequer, J-L.; Oberleithner, H.; Navajas, D. & Radmacher, M., Standardized Nanomechanical Atomic Force Microscopy Procedure (SNAP) for Measuring Soft and Biological Samples. Scientific Reports, 7:5117, DOI:10.1038/s41598-017-05383-0.
- Rigato, A., Miyagi, A., Scheuring, S. and Rico, F*. (2017). High-frequency microrheology reveals cytoskeleton dynamics in living cells. Nature Physics (in press).
- News and views by Klaus Kroy.
- Rigato A, F Rico, F Eghiaian, M Piel, S Scheuring, Atomic Force Microscopy Mechanical Mapping of Micropatterned Cells Shows Adhesion Geometry-Dependent Mechanical Response on Local and Global Scales. ACS Nano, 9, 5846-5856 2015
- Rico F, L González, I Casuso, M Puig, and S Scheuring. High-speed force spectroscopy unfolds titin at the velocity of molecular dynamics simulations. Science 342 (6159), 741-743 2013
- News and views
- Matching Protein Experiments to Simulations – C&EN
- Unfolding to force – Nature Methods
- New technique to unfold biomolecules at high speed – ScienceDaily
- The Adventures of Titin – The Analytical Scientist
- Speeding up the experiment to fit the simulation – Chemistry World
- In Spanish
- News and views
- Rico F, L Picas, A Colom, N Buzhynskyy, and S Scheuring. The mechanics of membrane proteins is a signature of biological function. Soft Matter 9 (32), 7866-7873 2013
- Picas L, F Rico and S Scheuring. Direct measurement of the mechanical properties of lipid phases in supported bilayers. Biophys J 102 (1) L01-L03 2012
- Rico F, A. Oshima, P. Hinterdorfer, Y. Fujiyoshi, S. Scheuring, Two-Dimensional Kinetics of Inter-Connexin Interactions from Single-Molecule Force Spectroscopy. J Mol Biol 412, 72 2011
- Hozic A¶, F. Rico, A. Colom, N. Buzhynskyy, S. Scheuring, Nanomechanical Characterization of the Stiffness of Eye Lens Cells: A Pilot Study. Invest Ophthalmol Vis Sci 53, 2151 2012
- Rico F, C. Su and S Scheuring. Mechanical mapping of single proteins at the submolecular level Nano Letters 11 (9) 3983-6 2011
- Cover story in Microscopy and Analysis, January/February 2012
- Rico F*, C Chu, MH Abdulreda, Y Qin and VT Moy. Temperature dependence of integrin-mediated cell adhesion. Biophys J 99 (5) 1387-1396 2010
- Rico F* and VT Moy. Energy landscape roughness of the streptavidin-biotin interaction. J Mol Recognit 20 (6) 495-501 2007
- Rico F, P Roca-Cusachs, N Gavara, R Farré, M Rotger and D Navajas. Probing Mechanical Properties of Living Cells by Atomic Force Microscopy with Blunted Pyramidal Cantilever Tips. Phys Rev E 72 (2) 021914 2005
2017 – Habilitation à Diriger des Recheches, Aix-Marseille Université
2006 – PhD in Biophysics, University of Barcelona, Spain
Thesis title: Study of viscoelasticity and adhesion of human alveolar epithelial cells by atomic force microscopy. The importance of probe geometry. URL Thesis director: Prof. Daniel Navajas
2001 – MA in Scientific Communication, Pompeu Fabra University, Spain
1999 – BS in Physics, University Autonoma of Barcelona, Spain
2012 – 2013 Postdoc at U1006 INSERM & Aix-Marseille Université, Marseille
2009 – 2011 Marie Curie Postdoctoral Fellow at UMR168, Institut Curie, Paris, France
2006 – 2008 Fulbright Postdoctoral Fellow at Vincent T. Moy’s lab, Department of Physiology and Biophysics, University of Miami Miller School of Medicine, Miami, FL, USA