Hybrid cell-soft nanoparticles aggregates

Hybrid cell-soft nanoparticles aggregates

Influence of the elasticity and volume fraction of added nanoparticles on the spreading of cellular aggregates

Françoise M. Winnik (1,2)
1. Department of Chemistry and Faculty of Pharmacy, University of Montreal, CP 6128 Succursale Centre Ville, Montreal QC H3C3J7, Canada.
2. WPI International Center for Materials Nanoarchitectonics (MANA), National Institute for Materials Science, 1-1 Namiki, Tsukuba, Ibaraki 305-0044 Japan.
Collaboration : Françoise Brochard-Wyart (Curie Institute, Physical Chemistry Curie, UMR 168, UPMC, Paris, France)

We have been working for the last years on applying soft matter physics to study the biophysics of tissues (tissue rheology, aspiration, spreading, mechanosensitivity, wetting and dewetting, adhesion and fracture) using cellular aggregates are a model system.(1-4). They result from the aggregation of a few thousands of cells, and form spheroids because they act as a liquid and minimize their surface energy. While single cell migration has been studied extensively, much less is known about the migration of cell populations. We have studied and interpreted, by analogy with the physics of wetting, the dynamics of spreading of aggregates and the migration of cell clusters on solid and soft substrates (polymer gels). We have shown that the rigidity of the substrate controls the wetting transition, the spreading velocity and the migration of the whole aggregate.(7) Since aggregate spreading occurs during early embryonic development and is suspected to play a large roles in cancer metastasis, the results obtained from such analogies may have important implications in our understanding of both tissue development and cancer.
Recently we have focused on cellular aggregate – nanoparticles hybrid systems. It has been previously shown that nanoparticles can modify the mechanical properties of single cells in terms of adhesion area, proliferation and motility.(5-6) We have studied the spreading of hybrid cell-rigid nanoparticles aggregates and shown that they affect cell dispersion. In this project we will study how “jelly-like” particles can influence the collective cell behaviour.
We propose to study the cellular aggregate – nanoparticles system by varying the size, the shape and the elastic modulus of hydrophilic jelly particles (from kPa to MPa range) and the volume fraction Φ of the cells in this artificial matrix. The volume fraction Φ can be fixed during the aggregate fabrication, or Φ can increase with time by cell divisions. If Φ is small, we will follow the migrations of single cells in the matrix. When Φ increases, we will observe a fluidization of the aggregate at Φ=Φc. For Φ larger than Φc, we will study the dynamics of spreading versus the elastic modulus of the beads. We expect a modification of the cell-cell interactions if the nanoparticles act as glue between the cells, and an increase of the cohesion of the aggregates for stiffer particles. We will study both the statics and the dynamics of spreading of these hybrid aggregates.
The candidate will not be limited to this project and will have the opportunity to develop his/her own ideas in the field of cellular aggregates. The candidate should have a strong background in biophysics and be familiar with the chemistry of nanoparticles synthetized in the group of F.Winnik.

The position is for one year, renewable upon mutual agreement and is located in Tsukuba, Japan, at the MANA Center of NIMS (

Please send your CV, a letter of motivation and the name/address of three scientists who would be able to send a letter of evaluation to F. M. Winnik and F. Brochard-Wyart.

1. Guevorkian, K., Colbert, M.-J., Durth, M., Dufour, S. & Brochard-Wyart, F. Aspiration of Biological Viscoelastic Drops. Physical Review Letters 104, 1–4 (2010).
2. Guevorkian, K., Gonzalez-Rodriguez, D., Carlier, C., Dufour, S. & Brochard-Wyart, F. Mechanosensitive shivering of model tissues under controlled aspiration. Proceedings of the National Academy of Sciences of the United States of America 108, (2011).
3. Gonzalez-Rodriguez, D., Guevorkian, K., Douezan, S. & Brochard-Wyart, F. Soft matter models of developing tissues and tumors. Science (New York, N.Y.) 338, 910–7 (2012).
4. Beaune, G., Stirbat, T.-V., Khalifat, N., Cochet-Escartin, O., Garcia, S., Gurchenkov, V.-V., Murrell, M.-P., Sufour, S., Cuvelier, D. & Brochard-Wyart, F. How cells flow in the spreading of cellular aggregates. Proceedings of the National Academy of Sciences of the United States of America 111, (2014).
5. Yang, J.-A., Phan, H.-T., Vaidya, S. & Murphy, C.-J., Nanovacuums: Nanoparticle Uptake and Differential Cellular Migration on a Carpet of nanoparticles. Nano Letters 13, (2013).
6. Tay, C.-Y., Cai, P., Setyawati, M.-I., Fang, W., Tan, L.-P., Hong, C.H.L., Chen, X. & Leong, D.,-T., Nanoparticles strengthen intracellular tension and retard cellular migration. Nano Letters 14, (2014).
7. Douezan, S., Dumond, J. & Brochard-Wyart, F. Wetting transitions of cellular aggregates induced by substrate rigidity. Soft Matter 8, 4578 (2012).


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