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Investigating ligand-receptor interactions for the capture of circulating cells at the blood vessel wall

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This internship is part of the UGA Emergence Project “Cell Homing”, a multidisciplinary project that involves several laboratories (LIPhy, Département de Chimie Moléculaire and Institut Albert Bonniot in Grenoble, and CIC BiomaGUNE in San Sebastian, Spain) and aims at understanding how the glycan-rich layer covering blood vessels orchestrates biophysical and biochemical signals to regulate selective capture and traffic of cells from the circulation into tissues.

Cell homing from the blood circulation into tissues is a vital physiological process. The attraction of immune and stem cells is crucial for immune and inflammatory responses, and for tissue repair, respectively. The selective and coordinated cell entry through the endothelial cell layer is regulated by the endothelial surface layer (ESL), a soft and hydrated extracellular coat that lines the luminal surface of the vascular endothelium and that is strategically positioned to function as gate keeper for cell extravasation.

The linear polysaccharide hyaluronan (HA) is a key structural component of the ESL, providing for softness and deformability. HA molecules also contain binding sites for CD44, a cell surface receptor common to many circulating cells. HA-CD44 interactions are known to be involved in the recruitment of some immune cells, and in the migration of tumor cells. Cell attachment to HA has recently been reported to strengthen under flow, yet the underlying mechanism remains obscure. Here, our aim is to understand the physical origins of the unusual flow-enhanced adhesion, a crucial point in the regulation of cell capture. To this end, we will study biomimetic systems that reproduce selected properties of the ESL and circulating cells, but that are much better defined and thus allow for highly quantitative biophysical measurements that are not possible with the complex biological system.

This Master M2 Internship will take place at LIPhy. Over the course of the internship, you will be given the opportunity :

- to design, build and test the experimental setup (a microfluidic device) for laminar flow assays,

- to develop routines for the tracking of circulating cells or model microbeads under flow by optical microscopy, and/or

- apply these methods to quantify the lifetime of single CD44-HA bonds under tensile stress, using CD44-functionalized microbeads on HA-functionalized planar surfaces, and to study the influence of the number of CD44-HA bonds on the strength and lifetime of the bead-surface interaction.

Moreover, you will be able to develop interpersonal skills by working in a multidisciplinary project involving physicists, chemists and biologists.

Contact :

Delphine Débarre (delphine.debarre@ujf-grenoble.fr)& Lionel Bureau (+33 (0)4 76 51 47 63 ; lionel.bureau@ujf-grenoble.fr)