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Biology subjects

Lipp, C.

Publications and source records attributed to Lipp, C..

2 recordsLinked to original sources

Microfluidic device combining hydrodynamic and dielectrophoretic trapping for the controlled contact between single micro-sized objects and application to adhesion assays

The understanding of cell-cell and cell-matrix interactions via receptor and ligand binding relies on our ability to study the very first events of their contact. Of particular interest is the interaction between a T cell receptor and its cognate peptide-major histocompatibility complex. Indeed analyzing their binding kinetics and cellular avidity in large-scale low-cost and fast cell sorting would largely facilitate the access to cell-based cancer immunotherapies. We thus propose a microfluidic tool able to independently control two types of micro-sized objects, put them in contact for a defined time and probe their adhesion state. The device consists in hydrodynamic traps holding the first type of cells from below against the fluid flow, and a dielectrophoretic system to force the second type of object to remain in contact to the first one. First the device is validated by performing an adhesion frequency assay between fibroblasts and fibronectin coated bead. Then, a study is conducted on the modification of the cellular environment to match the dielectrophoretic technology requirements without modifying the cells viability and interaction functionalities. Finally, we demonstrate the capability of the developed device to put cancer cells and a population of T cells in contact and show the discrimination between specific and non specific interactions based on pairs lifetime.

bioengineering↗

The impact of size on particle drainage dynamics and antibody response

Vaccine-induced immune response can be greatly enhanced by mimicking pathogen properties. The size and the repetitive geometric shape of virus-like particles (VLPs) influence their immunogenicity by facilitating drainage to secondary lymphoid organs and enhancing interaction with and activation of B-cells and other innate humoral immune components. VLPs derived from the plant Bromovirus genus, specifically cowpea chlorotic mottle virus (CCMV), are T=3 icosahedron particles. They can be easily expressed in an E. coli host system and package ssRNA during the expression process. Recently, we have engineered CCMV-VLPs by incorporating the universal tetanus toxoid (TT) epitope at the N-terminus. The modified CCMVTT-VLPs successfully form icosahedral particles T=3, with a diameter of [~]30nm analogous to the parental VLPs. Interestingly, incorporating TT epitope at the C-terminus of CCMVTT-VLPs results in the formation of Rod-shaped VLPs, [~]1{micro}m in length and [~]30nm in width. In this study, we have investigated the draining kinetics and immunogenicity of both engineered forms (termed as Round-shaped CCMVTT-VLPs and Rod-shaped CCMVTT-VLPs) as potential B cell immunogens using different in vitro and in vivo assays. Our results reveal that Round-shaped CCMVTT-VLPs are more efficient in draining to secondary lymphoid organs to charge antigen-presenting cells as well as B-cells. Furthermore, compared to Rod-shaped CCMVTT-VLPs, Round-shaped CCMVTT-VLPs led to more than 100-fold increased systemic IgG and IgA responses accompanied by prominent formation of splenic germinal centers. Round-shaped CCMVTT-VLPs could also polarize the induced immune response towards TH1. Up to our knowledge, this is the first study investigating and comparing the draining kinetics and immunogenicity of one and the same VLP monomer forming nano-sized icosahedrons or rods in the micrometer size.

immunology↗