📋 Tender Overview
Impact Of Cell Shapes On Cell Behaviour And Fate
A Closer Look At How Cellular Memory Effects Immunity And Cancerduring Tissue Growth And Overgrowth, Changes In Tissue Environments Lead To Alterations In Cell Shape, Resulting In Deformations. Cells Exhibit Adaptability To These Shape Changes, Both In Migratory Cells And During Cancer Metastases. However, Little Is Known About The Related Mechanisms And Implications. The Erc-Funded Shapincellfate Project Postulates That Cells Retain A Memory Of Their Mechanical And Geometrical History, Which Influences Their Developmental Trajectory. It Will Study The Molecular Mechanisms And Physical Principles That Underlie These Memory Effects Induced By Changes In Cell Shape. It Will Also Study How These Impact Immunity And Cancer. The Focal Points Of This Research Are Dendritic Cells And Cancer Cells Originating From Mammary Epithelia.
Funded Under
European Research Council (Erc)
Total Cost
€ 10 834 795,00
Eu Contribution
€ 10 834 795,00
Coordinated By
Centre National De La Recherche Scientifique Cnrs
France
Objective
Cells are often depicted as irregular spherical objects - the shape they adopt in suspension. However, the packed environment of tissues alters this simple shape, causing large cell deformations. This occurs during normal tissue growth and is even more pronounced upon tissue overgrowth, as in the case of solid tumors. Cell shape changes frequently occur in migratory cells, such as immune cells that patrol the organism within interstitial tissues, and cancer metastases that escape from the primary tumor to invade healthy tissues. In all cases, cells adapt and survive even to very large deformations. The mechanisms underlying such response and the long-term consequences that repeated cell shape changes have on physiology and pathology remain largely unknown.
We have observed that changes in the shape of cells and organelle(s) induce reversible and irreversible modifications in their behaviour and function(s). We hypothesize that cells use such mechanisms to integrate the successive deformations of distinct amplitudes and durations that they experience during their lifetime. This implies the existence of shape-induced memory effects that not only encode the geometrical and mechanical history of the cell but also dictate its fate. Here, we propose to tackle the molecular mechanisms and physical principles accounting for shape-induced memory effects and to evaluate their impact on immunity and cancer. We will focus on two cell types that undergo large shape changes in vivo, and communicate to establish cancer immunity: (1) dendritic cells, which initiate adaptive immune responses, and (2) cancer cells derived from mammary epithelia. Our project will reveal whether boundary conditions imposed by physical confinement are overarching determinants of cellular behaviours at different spatial and temporal scales, and may further establish novel clinical paths for a holistic understandi
