Nanoparticles to modulate topography and ligand distribution at the nanoscale: impact on cell behavior

Abstract

Understanding cell-material interactions is an important goal for the development of tissue engineering strategies, either to treat diseases or to replace missing or damaged tissues or organs. The interaction of cell with matter is driven through biochemical and mechanical signals received from the environment which must be transmitted across the cell membrane. Among those signals, topography and ligand distribution at the nanoscale have been proved to be relevant in cell biology. In this work, using a nanoarchitectonic approach involving molecular self-assembly, different kinds of organic nanoparticulate materials have been processed on surfaces to produce biofunctionalized substrates to better understand and control cell behavior._x000D_ Inclusion body-like protein nanoparticles (IB-like pNPs) are aggregates of protein produced in bacterial hosts. These aggregates have the characteristics of a soft nanoparticulate material that retains the function of the original protein. In chapter 2, IB-like pNPs have been used to biofunctionalize and modulate the topography of surfaces at the nanoscale to control cell behavior. Specifically, pNPs have been covalently anchored on maleimide-terminated self-assembled monolayers (SAMs) exploiting the maleimide-thiol click reaction. Additionally, the pNPs have been arranged into striped micropatterns through microcontact printing, being able to successfully guide cell adhesion and morphology._x000D_ Quatsomes are non-liposomal lipid-based nanovesicles, developed by the Nanomol-Bio group, formed by self-assembly of surfactants and sterols. Quatsomes exhibit high vesicle-to-vesicle homogeneity and high stability and shelf life. Additionally, their membrane is fluid, allowing for a lateral diffusion of molecules anchored to their membranes. In chapter 3, Quatsomes have been used as organic nanoparticles to modulate the topography and cell adhesion ligand distribution at the nanoscale enhancing integrin mediated cell adhesion. Specifically, Quatsomes decorated with cell adhesion ligands, RGD peptides, have been anchored on surfaces in a state of quasi-suspension through a gold-thiol interaction. The novel nanoarchitectonic surfaces exhibit an enhancement of focal adhesions in comparison to conventional surfaces with homogeneously distributed ligands on surfaces._x000D_ Finally, in chapter 4, Quatsomes have been explored as candidates to control the ligand distribution at the nanoscale and impact cell behavior in a 3D environment. Thus, Quatsomes have been integrated in hybrid PEG-heparin hydrogels to be used as artificial lymph nodes, in order to improve the proliferation of immune cells for adoptive cell therapies._x000D_ In summary, the work carried out in this thesis offers new possibilities to control topography and ligand distribution at the nanoscale using different organic nanoparticles, enhancing the impact on cell behavior in 2D and 3D environments for cell biology and tissue engineering applications.

Date of Award	9 Mar 2023
Original language	English
Supervisor	Leonor Ventosa Rull (Director), Imma Ratera Bastardas (Director) & Judit Guasch Camell (Director)