Development of experimental systems for studying the interaction between nanoparticles and model lipid bilayers

The internship will take place within the nanomedicine team at LVTS, primarily at the SMBH Faculty of Université Sorbonne Paris Nord, at Bobigny. This multidisciplinary team includes physicists, chemists, biologists and clinicians specializing in the development and characterization of nanoparticles for biomedical applications. 

Additionally, the intern will carry out part of the characterization work at external facilities, including TEM (Transmission Electron Microscopy) at the Institut Jacques Monod and SAXS (Small-Angle X-ray Scattering) at the CEA in Saclay. The intern will also present the project to LVTS members at Bichat Hospital. 

The use of nanomaterials for medical applications, such as drug delivery, diagnostics, or as contrast agents for medical imaging, is a highly active area of research in both academic and industrial settings [1], [2], [3]. Additionally, the industrial use of nanomaterials in various sectors and their dissemination into the environment raise important questions about human and environmental toxicology [4]. 

The biological cell, the fundamental building block of all living organisms, is surrounded by the plasma membrane, which serves as a barrier and regulates the exchange of matter, energy, and information. Understanding how nanoparticles (NPs) interact with and potentially cross this membrane is crucial both for both optimizing their medical use and addressing toxicological concerns. Given the biochemical complexity of biological membranes, which makes them challenging to study, a "bottom-up" approach has been developed: simplified membranes, known as model lipid bilayers, are reconstructed in vitro using phospholipids, the fundamental building blocks of biological membranes. This approach enables the control over their composition and environment, allowing the study of various parameters independently, and the use of characterization methods which are incompatible with in vivo conditions [5]. 

The goal of this internship is to develop further the experimental systems existing in the lab for characterization of the interaction between NPs and model lipid bilayers. This development will require the use of fluorescence microscopy and electrical impedance spectroscopy (see Figure). Even if the focus of this internship is experimental, a theoretical model will be used to understand the experimental results.

Depending on the funding availabe and the motivation of the candidate, a Ph.D. position might be available at the end of this internship for candidates interested in a Ph.D. position.

Tasks :

• Literature review. 
• Improving the experimental systems. 
• Preparation of fluorescently labeled model lipid bilayers. 
• Daily update of the laboratory notebook. 
• Software optimization: optimizing the software used for experiment control, data acquisition and analysis (using Python). 
• Nanoparticle synthesis and characterization using techniques such as UV-Vis spectroscopy, DLS (Dynamic Light Scattering), SAXS (Small-Angle X-ray Scattering), TEM (Transmission Electron Microscopy), and zeta potential measurements. 
• Data Analysis and Processing (using Python). 
• Communication of the results (conferences, thesis writing, oral presentations). 

References:

C. Zhang et al., “Progress, challenges, and future of nanomedicine,” Nano Today, vol. 35, p. 101008, Dec. 2020, doi: 10.1016/j.nantod.2020.101008. 

[2] Y. Yi, M. Yu, W. Li, D. Zhu, L. Mei, and M. Ou, “Vaccine-like nanomedicine for cancer immunotherapy,” Journal of Controlled Release, vol. 355, pp. 760–778, Mar. 2023, doi: 10.1016/j.jconrel.2023.02.015. 

[3] W. C. W. Chan et al., “Noble Nanomedicine: Celebrating Groundbreaking mRNA Vaccine Innovations,” ACS Nano, vol. 17, no. 20, pp. 19476–19477, Oct. 2023, doi: 10.1021/acsnano.3c09781. 

[4] E. A. Kumah, R. D. Fopa, S. Harati, P. Boadu, F. V. Zohoori, and T. Pak, “Human and environmental impacts of nanoparticles: a scoping review of the current literature,” BMC Public Health, vol. 23, p. 1059, Jun. 2023, doi: 10.1186/s12889-023-15958-4. 

[5] C. Siontorou, G.-P. Nikoleli, D. Nikolelis, and S. Karapetis, “Artificial Lipid Membranes: Past, Present, and Future,” Membranes, vol. 7, no. 3, p. 38, Jul. 2017, doi: 10.3390/membranes7030038. 

• Basic laboratory skills, e.g. solution preparation, pH measurement, dilutions, etc. 
• General knowledge in biology, biophysics, physics, and biochemistry. 
• Programming skills (ideally in Python). 
• Teamwork: ability to collaborate effectively with team members. 
• Interest in experimental work: enthusiasm for hands-on experimental tasks.