https://sam.ensam.eu:443 The DSpace digital repository system captures, stores, indexes, preserves, and distributes digital research material. Sun, 12 Apr 2026 20:18:47 GMT 2026-04-12T20:18:47Z http://hdl.handle.net/10985/17464 A Coupled Friction-Poroelasticity Model of Chimneying Shows that Confined Cells Can Mechanically Migrate Without Adhesions MONDESERT-DEVERAUX, Solenne; ALLENA, Rachele; AUBRY, Denis Cell migration is the cornerstone of many biological phenomena such as cancer metastasis, immune response or organogenesis. Adhesion-based motility is the most renown and examined motility mode, but in an adhesion-free confined environment or simply to achieve a higher migration speed, cells can adopt a very interesting bleb-based migration mode called “chimneying”. This mode rests on the sharp synchronization between the active contraction of the cells uropod and the passive friction force between the cell and the confining surface. In this paper, we propose a one dimensional poroelastic model of chimneying which considers the active strains of the cell, but, as an improvement with respect to our previous works, the synchronization between such strains and the friction forces developed by the cell and necessary to move forward is self-determined. The present work allows to deepen our knowledge on chimneying which is still poorly understood from a mechanical point of view. Furthermore, our results emphasize the key role of poroelasticity in bleb formation and give new insights on the location and the time-synchronization of the friction force. Further development of this exploratory work could provide a major tool to test hypotheses beforehand and thus focus future experiments on mechanically relevant ones. Mon, 01 Jan 2018 00:00:00 GMT http://hdl.handle.net/10985/17464 2018-01-01T00:00:00Z MONDESERT-DEVERAUX, Solenne ALLENA, Rachele AUBRY, Denis Cell migration is the cornerstone of many biological phenomena such as cancer metastasis, immune response or organogenesis. Adhesion-based motility is the most renown and examined motility mode, but in an adhesion-free confined environment or simply to achieve a higher migration speed, cells can adopt a very interesting bleb-based migration mode called “chimneying”. This mode rests on the sharp synchronization between the active contraction of the cells uropod and the passive friction force between the cell and the confining surface. In this paper, we propose a one dimensional poroelastic model of chimneying which considers the active strains of the cell, but, as an improvement with respect to our previous works, the synchronization between such strains and the friction forces developed by the cell and necessary to move forward is self-determined. The present work allows to deepen our knowledge on chimneying which is still poorly understood from a mechanical point of view. Furthermore, our results emphasize the key role of poroelasticity in bleb formation and give new insights on the location and the time-synchronization of the friction force. Further development of this exploratory work could provide a major tool to test hypotheses beforehand and thus focus future experiments on mechanically relevant ones. http://hdl.handle.net/10985/17461 In silico approach to quantify nucleus self‑deformation on micropillared substrates MONDESERT-DEVERAUX, Solenne; ALLENA, Rachele; AUBRY, Denis Considering the major role of confined cell migration in biological processes and diseases, such as embryogenesis or metastatic cancer, it has become increasingly important to design relevant experimental set-ups for in vitro studies. Microfluidic devices have recently presented great opportunities in their respect since they offer the possibility to study all the steps from a suspended to a spread, and eventually crawling cell or a cell with highly deformed nucleus. Here, we focus on the nucleus self-deformation over a micropillared substrate. Actin networks have been observed at two locations in this set-up: above the nucleus, forming the perinuclear actin cap (PAC), and below the nucleus, surrounding the pillars. We can then wonder which of these contractile networks is responsible for nuclear deformation. The cytoplasm and the nucleus are represented through the superposition of a viscous and a hyperelastic material and follow a series of processes. First, the suspended cell settles on the pillars due to gravity. Second, an adhesive spreading force comes into play, and then, active deformations contract one or both actin domains and consequently the nucleus. Our model is first tested on a flat substrate to validate its global behaviour before being confronted to a micropillared substrate. Overall, the nucleus appears to be mostly pulled towards the pillars, while the mechanical action of the PAC is weak. Eventually, we test the influence of gravity and prove that the gravitational force does not play a role in the final deformation of the nucleus. Tue, 01 Jan 2019 00:00:00 GMT http://hdl.handle.net/10985/17461 2019-01-01T00:00:00Z MONDESERT-DEVERAUX, Solenne ALLENA, Rachele AUBRY, Denis Considering the major role of confined cell migration in biological processes and diseases, such as embryogenesis or metastatic cancer, it has become increasingly important to design relevant experimental set-ups for in vitro studies. Microfluidic devices have recently presented great opportunities in their respect since they offer the possibility to study all the steps from a suspended to a spread, and eventually crawling cell or a cell with highly deformed nucleus. Here, we focus on the nucleus self-deformation over a micropillared substrate. Actin networks have been observed at two locations in this set-up: above the nucleus, forming the perinuclear actin cap (PAC), and below the nucleus, surrounding the pillars. We can then wonder which of these contractile networks is responsible for nuclear deformation. The cytoplasm and the nucleus are represented through the superposition of a viscous and a hyperelastic material and follow a series of processes. First, the suspended cell settles on the pillars due to gravity. Second, an adhesive spreading force comes into play, and then, active deformations contract one or both actin domains and consequently the nucleus. Our model is first tested on a flat substrate to validate its global behaviour before being confronted to a micropillared substrate. Overall, the nucleus appears to be mostly pulled towards the pillars, while the mechanical action of the PAC is weak. Eventually, we test the influence of gravity and prove that the gravitational force does not play a role in the final deformation of the nucleus. http://hdl.handle.net/10985/18418 High-throughput microfluidic micropipette aspiration device to probe time-scale dependent nuclear mechanics in intact cells DAVIDSON, Patricia M; FEDORCHAK, Gregory R; MONDESERT-DEVERAUX, Solenne; BELL, Emily S; ISERMANN, Philipp; AUBRY, Denis; ALLENA, Rachele; LAMMERDING, Jan The mechanical properties of the cell nucleus are increasingly recognized as critical in many biological processes. The deformability of the nucleus determines the ability of immune and cancer cells to migrate through tissues and across endothelial cell layers, and changes to the mechanical properties of the nucleus can serve as novel biomarkers in processes such as cancer progression and stem cell differentiation. However, current techniques to measure the viscoelastic nuclear mechanical properties are often time consuming, limited to probing one cell at a time, or require expensive, highly specialized equipment. Furthermore, many current assays do not measure time-dependent properties, which are characteristic of viscoelastic materials. Here, we present an easy-to-use microfluidic device that applies the well-established approach of micropipette aspiration, adapted to measure many cells in parallel. The device design allows rapid loading and purging of cells for measurements, and minimizes clogging by large particles or clusters of cells. Combined with a semi-automated image analysis pipeline, the microfluidic device approach enables significantly increased experimental throughput. We validated the experimental platform by comparing computational models of the fluid mechanics in the device with experimental measurements of fluid flow. In addition, we conducted experiments on cells lacking the nuclear envelope protein lamin A/C and wild-type controls, which have well-characterized nuclear mechanical properties. Fitting time-dependent nuclear deformation data to power law and different viscoelastic models revealed that loss of lamin A/C significantly altered the elastic and viscous properties of the nucleus, resulting in substantially increased nuclear deformability. Lastly, to demonstrate the versatility of the devices, we characterized the viscoelastic nuclear mechanical properties in a variety of cell lines and experimental model systems, including human skin fibroblasts from an individual with a mutation in the lamin gene associated with dilated cardiomyopathy, healthy control fibroblasts, induced pluripotent stem cells (iPSCs), and human tumor cells. Taken together, these experiments demonstrate the ability of the microfluidic device and automated image analysis platform to provide robust, high throughput measurements of nuclear mechanical properties, including time-dependent elastic and viscous behavior, in a broad range of applications. Tue, 01 Jan 2019 00:00:00 GMT http://hdl.handle.net/10985/18418 2019-01-01T00:00:00Z DAVIDSON, Patricia M FEDORCHAK, Gregory R MONDESERT-DEVERAUX, Solenne BELL, Emily S ISERMANN, Philipp AUBRY, Denis ALLENA, Rachele LAMMERDING, Jan The mechanical properties of the cell nucleus are increasingly recognized as critical in many biological processes. The deformability of the nucleus determines the ability of immune and cancer cells to migrate through tissues and across endothelial cell layers, and changes to the mechanical properties of the nucleus can serve as novel biomarkers in processes such as cancer progression and stem cell differentiation. However, current techniques to measure the viscoelastic nuclear mechanical properties are often time consuming, limited to probing one cell at a time, or require expensive, highly specialized equipment. Furthermore, many current assays do not measure time-dependent properties, which are characteristic of viscoelastic materials. Here, we present an easy-to-use microfluidic device that applies the well-established approach of micropipette aspiration, adapted to measure many cells in parallel. The device design allows rapid loading and purging of cells for measurements, and minimizes clogging by large particles or clusters of cells. Combined with a semi-automated image analysis pipeline, the microfluidic device approach enables significantly increased experimental throughput. We validated the experimental platform by comparing computational models of the fluid mechanics in the device with experimental measurements of fluid flow. In addition, we conducted experiments on cells lacking the nuclear envelope protein lamin A/C and wild-type controls, which have well-characterized nuclear mechanical properties. Fitting time-dependent nuclear deformation data to power law and different viscoelastic models revealed that loss of lamin A/C significantly altered the elastic and viscous properties of the nucleus, resulting in substantially increased nuclear deformability. Lastly, to demonstrate the versatility of the devices, we characterized the viscoelastic nuclear mechanical properties in a variety of cell lines and experimental model systems, including human skin fibroblasts from an individual with a mutation in the lamin gene associated with dilated cardiomyopathy, healthy control fibroblasts, induced pluripotent stem cells (iPSCs), and human tumor cells. Taken together, these experiments demonstrate the ability of the microfluidic device and automated image analysis platform to provide robust, high throughput measurements of nuclear mechanical properties, including time-dependent elastic and viscous behavior, in a broad range of applications.