The LTM (Laboratory of the Technologies of Microelectronics, Grenoble) has a unique expertise in the design of substrates for 2D cell culture that exhibit controlled mechanical properties mimicking the mechanical properties of human tissues at the micron scale (micrometer being the scale of cell adhesive spots on their matrix). These substrates are currently used at the LTM for the study of cell behavior in the context of oncology and regenerative medicine. These technologies would benefit from being pushed to 3D to gain in tissue mimicry, as it is known that cell responses differ between 2D and 3D geometries.
The goal of the internship is to contribute to the implementation of this increased complexity. To this end, the work will consist in developing technological processes to design 3D scaffolds for cell culture with tunable physical properties at the micron scale using 3D optical lithography techniques: for instance, 3D controlled stiffness or gradients of stiffness, 3D specific geometries, 3D actuable substrates, etc. Cellular tests will also be performed during the internship in the context of fundamental knowledge in cell biology, oncology or stem cell differentiation.
Two lithographic tools will be made available for the training: a DLP 3D printer and a two-photon polymerization direct laser writing tool. The intern will also benefit from access to clean rooms and cell culture facilities available at LTM, in partnership with CEA Léti.
The intern will first have to lead an extensive bibliographic work on technologies dedicated to the design of 3D scaffolds for cell culture and their applications. Special attention will be paid to soft or actuable scaffolds. The work will then consist in developing 3D printing and 2-photon lithography processes for soft materials, either hydrogels or soft elastomers, whose rigidity is similar to that of human tissues, of order of few kiloPascal. Soft scaffolds will then be designed having specific physical properties, for instance specific geometrical feature that could be relevant for the study of cell adaptation to stiffness in 3D environments (normal, tumor or stem cells) or be actuable, e.g. by the application of a magnetic field, with could help in the generation of mature muscular or cardiac cells.
During the internship, the trainee will gain scientific skills in micro and nanofabrication techniques, physico-chemistry of optical lithography, basics of elasticity, optical microscopy (standard and confocal), Scanning Electron Microscopy, cell mechanics, cell culture, cell staining (immunostaining and transfection).
The internship takes place in the team Micro and Nanotechnologies for Health, Energy and Environment, which has about 25 people. He/she will be supervised by a physico-chemist (J. H. Tortai) with an extended expertise in micro and nanotechnologies for microelectronics and by a biophysicist (A. Nicolas) who has expertise in adapting technologies from microelectronics to biophysical topics.
Relevant publications:
S. Palva, et al. ACS Biomat. Sci. Eng., 6:340-351, 2020. http://dx.doi.org/10.1021/acsbiomaterials.9b01189
A. Mgharbel, et al. Nanomaterials, 12: 648, 2022. http://dx.doi.org/10.3390/nano12040648
Webpage:
https://ltmlab.fr/biophysics-of-cell-adhesion/
Program, or background and skills expected: Master in
Soft Nanosciences or
Phelma Biomedical Engineering
Expected scientific skills: good understanding of the basics of fundamental physics at BSc level (mechanics, optics, magnetism). Some basic knowledge on polymerization processes and/or on cell biology will be appreciated.
Expected human skills: rigor, curiosity, critical analysis, decision-making ability, sociability
