Welcome to the Research Group Tissue Mechanobiology
About the group and its vision
Detection and transduction of mechanical signals at the cellular level are essential activities which control the shape and function of an organism and are compromised in certain diseases such as cancer or cardiovascular issues. The forces and mechanical properties of the environment are the parameters detected by cells. Mechanobiology thus encompasses all approaches demonstrating that the majority of biological processes, at scales ranging from molecules to organisms, are sensitive to mechanical constraints. Several foundations of this discipline are found in a treatise published by D’Arcy Thompson in 1917, "On Growth and Form," postulating that morphogenesis can be explained by forces and movements. Our research is at the interface between physics and biology.
What is the subject of the research?
In this context, our team studies the physical principles governing the self-organization of cellular and tissue systems as well as their adaptation to mechanical constraints of the environment. We develop new technologies to mimic in vivo mechanisms, map, and disrupt the physical properties which determine the growth, movement, invasion, and remodeling of cells and tissues. By combining this physical information with molecular perturbations and theoretical models, we explore the principles governing the interaction between chemical and physical signals in living tissues.
What are the pressing issues being researched?
Our research aims at understanding how cell adhesion-associated mechanotransduction and mechanosensing regulates cell behavior and tissue mechanics. In this context, we are studying how the cooperation between adhesion, mechanical and biochemical signaling leads to the adaptation of living cells to changes in their physical environment at various scales, from single molecules to tissues. We conduct innovative studies to characterize and model the biomechanical properties of epithelial tissues. Our primary focus is on collective movements within epithelial sheets, wound healing, and cell extrusion.
Why is this relevant?
The general field of mechanobiology is currently evolving toward more integrated research between physics, biology, chemistry and medicine, and the combination of in vitro and in vivo expertise. Our research has implications for physiological and pathological processes including morphogenesis, wound healing, ageing and cancer metastasis.
Research Overview
Collective cell migration
We study the mechanisms underlying collective cell behaviors. Our objective is to decipher, from the viewpoints of both physics and biology, how force transmission and biomechanical signalling at cell-cell contacts support multi-scale polarization. We aim to identify how force generation by the cytoskeleton and intercellular force transmission participates in cell polarization and coordination during epithelial collective cell migration in simplified model systems in vitro. We explore the emergence of cell polarization from the single cell up to multicellular assemblies. We analyse how mechanical coupling at cell contacts induces symmetry breaking beyond the single cell level, characterize coordinated polarization emerging during collective cell migration, and determine how intercellular mechano-chemical cues regulate polarization at the tissue scale.
Tissue homeostasis and cell extrusion.
Epithelia are assemblies of multiple cells whose complex dynamic behavior relies on physical properties including jamming-unjamming mechanisms, active turbulence and active nematic principles. The homeostasis of epithelia is crucial to maintaining barrier function and integrity while epithelial cells are constantly challenged by the environment. To face these challenges, epithelia are dynamic and have to deal constantly with cell renewal and extrusion, whose balance is key for epithelia homeostasis. In addition to this role in tissue homeostasis, cell extrusion is a major cause of tissue shape changes and tumor progression. We study how these mechanical constraints arising from the active forces generated by neighboring cells and the passive physical properties of the environment can determine the modes of cell extrusion and the fate of extruded cells.
Cellular monolayers as active nematics
Our research has drawn on the analogy between the active nature of biological tissues and nematic liquid crystals to gain a deeper understanding of how cells collectively self-organise. Like liquid crystals, cell populations can be arranged parallel to each other, with their 'long' sides all pointing in the same direction. Following this analogy, they also exhibit areas of misalignment known as 'topological defects'. We study how these physical properties can alter tissue dynamics including adhesion, integrity, and movement.
Cell rheology
We investigate the relationship between rheological properties of the cytoskeleton and matrix stiffness, simultaneously tracking cytoskeletal organization, tensile forces, and cellular responses. We develop micromechanical tools to analyze the cellular adaptation to external stimuli.
Cell competition
Cell competition is a tissue surveillance mechanism important in development, infection pathology and tumorigenesis. In these processes, cells with reduced fitness compared to their surrounding sare outcompeted and eliminated. We investigate cell competition in mixed cell populations using extensive cellular models to understand the potential contribution of mechanics to this process.
Contact
Principal Investigator Professor Benoît Ladoux
Max-Planck-Zentrum für Physik und Medizin
Kussmaulallee 2
91054 Erlangen, Germany
Professor Benoît Ladoux
"Not only are there wrong answers, there are also wrong questions.”
– Gilles Deleuze
