Influence of the cell surface glycocalyx and of the protein corona on the cellular adhesion and internalization of polystyrene nanoparticles

• Grant number: 19/20362-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: December 01, 2019
• End date: August 31, 2022
• Field of knowledge: Biological Sciences - Biophysics - Cellular Biophysics
• Principal Investigator: Alioscka Augusto Sousa
• Grantee: Isabela Ferreira de Assis
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

In the last decades, several studies have been undertaken to characterize the cell internalization of synthetic nanoparticles (NPs). On the one hand, part of these studies have attempted to obtain in-depth understanding of the physicochemical, cellular and environmental factors governing the uptake of NPs, with implications for the use of NPs as nanocarriers of drugs or other compounds in biomedical applications. In addition, NPs have been also employed as model systems and tools to provide new insights into the cell biology of endocytosis. However, despite all the progress so far, there are still many unknowns regarding how synthetic NPs interact with cells and are eventually endocytosed. For example, the influence of the cell surface glycocalyx on NP-cell interactions has been mostly overlooked so far. This is surprising considering the > 1 mM length of the glycocalyx, its highly overall negative charge, and its biochemical and structural complexity. Presumably, the glycocalyx may function either as a barrier to prevent direct NP-membrane binding, or as a dense network that helps entrap and accumulate NPs at the plasma membrane to facilitate their internalization. Given the above considerations, here the role of the surface glycocalyx on the cellular binding and internalization of model polystyrene NPs will be investigated. A wildtype and a mutant (glycosaminoglycan-deficient) CHO cell line will be used in the studies. In addition, the NPs will be placed in the presence of excess albumin and the ensuing albumin corona will be characterized in terms of its amount, adhesion strength to the NP surface and structural conformation. Taken together, the results from these studies will be utilized to propose a NP-cell interaction model incorporating explicitly the role of the glycocalyx in conjunction with that of the protein corona on the interactions. (AU)