Confinement, or the lack of space, is a common feature affecting cells within tissues, but its effects are poorly studied at the single cell level. Confinement can impose strong cell deformations, over a variety of timescales from seconds to days. It can result from normal tissue growth, or overgrowth in tumors, over hours or days. It can also result from the migratory activity of immune and metastatic cells between other cells or through interstitial tissues, which corresponds to deformations over minutes to hours. Finally, fast tissue deformation or circulation of cells through small capillaries can impose deformations at the scale of seconds. We have developed a series of tools with which we can impose controlled cell deformations over different timescales, or through which cells can spontaneously deform while migrating. We found that cell deformation can result in fast cell responses, such as activation of myosin contractility, loss of up to 40% of cell and nuclear volume, but also have long term consequences such as switching to a persistent blebbing mode, or even affect cell fate, following prolonged nuclear envelope rupture and DNA damage. Cell response to confinement might prove to be an important part of normal and pathological cell physiology. While the cell cytoplasm appears to be fluid even on short timescale, it is not the case of the nucleus. Here I will focus on consequences of confinement on the cell nucleus and how this organelle contributes to medium and long term cell response to deformation.


Seminar, December 13, 2017, 12:00. ICFO’s Seminar Room