Research axes

Dynamics of membrane proteins and membrane remodeling, in health and disease

We are aiming to understand how proteins and lipids interact to drive membrane domains formation, membrane deformation, fusion and fission and how membrane heterogeneity generates complexity and biological function. Using in vitro reconstituted systems, we explore the physical and biochemical rules governing membrane dynamics. Our focus includes how antimicrobial peptides disrupt bacterial membranes (with potential pharmaceutical applications), how calcium triggers exocytosis, and how voltage-gated ion channels and ceramides alter membrane structure.

Protein-protein and protein-lipid interactions at the neuronal synapse

We investigate two key players:

• Botulinum neurotoxin B receptors — these toxins, used therapeutically, hijack a transient and dynamic preassembled synaptic protein/lipid complex (synaptotagmin/ganglioside). We aim to understand the physiological importance of this preassembled complex in the life cycle of synaptic vesicles and study its spatial organization with native synaptic partners.
• LGI1 (Leucin-rich Glioma Inactivated 1) — the expression level of this protein is important in stabilizing membrane Kv1 potassium channels. Partial decrease of LGI1 in genetic haploinsufficiencies as well as autoimmune attacks leads respectively to genetic and autoimmune limbic encephalitis with perturbation in neuronal excitability. We aim to understand the molecular pathways through which LGI1 stabilises membrane Kv1.

Single molecule and membrane mechanics

Membrane interaction with their surroundings is mediated by molecules. Using advanced tools like atomic force microscopy and acoustic force spectroscopy, we characterize these interactions at the single-molecule level, revealing how forces and mechanics influence membrane behavior. Single molecule measurements are complemented with bulk, ensemble measurements using surface plasmon resonance. Additionally, we aim to deepen our understanding of the mechanics of membranes and how it modulates membrane protein dynamics and interactions.

Multiscale adhesion and mechanics in cell function

Adhesion and mechanics are deeply interrelated. We investigate how mechanical forces and adhesion shape two key processes: cancer metastasis and the leukocyte adhesion cascade. Cancer cells are known to become softer as they turn malignant, which changes the interaction with their nanoenvironment. Meanwhile, immune cells support mechanical forces to adhere to blood vessel walls, leading to the formation of membrane tethers and remodelling their cytoskeleton. To understand these processes, we use nanotools to characterize the adhesion and mechanical properties across length and time scales — from single molecules to whole cells and from microseconds to hours.

Cancer stem cells and microenvironment mechanics

Mechanical signals are now recognized as crucial regulators of cell fate and function. Our research focuses on stem cells and their pathological counter-part cancer stem cells. We are studying how mechanical cues maintain stemness or tumor progression. This new field of research, called rheo-histology, aims to uncover new insights about tissue organization and function, beyond traditional 3D structure.

Fundamental mechanical response of single molecules, membranes, cells and tissues

Cells and tissues display complex, heterogeneous mechanical behaviors that are essential for their biological function. To unravel these responses, we develop innovative techniques, approaches, models and protocols at the nano- and micro-scales, spanning a broad range of timescales. Our aim is to construct a mechanistic understanding of how cells and their molecular components respond to mechanical forces, thereby bridging the gap between single molecules and whole tissues.

Biological systems organize themselves across scales, from molecules to organisms and ecosystems, through a cascade of emergent processes. Our research bridges statistical physics, biology, and soft-matter theory, exploring how order and function arise at each level.

Through multidisciplinary collaborations, we investigate a range of biophysical questions:

• How metabolism and morphogenesis shape tissue mechanics and pattern formation
• The bioenergetics and evolution of biomolecular networks
• Strategies to control stochastic processes in biology, from single cells to populations
• The role of phase separation and transport in active biological mixtures

By integrating theory and experiment, we aim to uncover the universal principles governing life's complexity.

A defining strength of our lab is our capacity for innovation, development and application of nanotechnology tools — particularly atomic force microscopy (AFM) techniques, which we complement with traditional approaches.

As one of the pioneer laboratories of high-speed atomic force microscopy (HS-AFM) and high-speed force spectroscopy (HS-FS), we use these unique nanotools for label-free imaging of molecular dynamics at the nanoscale. Our methods allow us to probe the mechanics of biomolecules, membranes and cells with submicrosecond time resolution.

We have recently integrated acoustic force spectroscopy (AFS) into our toolkit, enabling us to probe single molecule receptor-ligand interactions at ultraslow loading rate and to investigate the mechanics of living cells at low frequencies. 

We are also improving and developing new molecular force sensors to probe intercellular forces in living systems.