Maryam MOMTAZ
E-mail : momtaz@chim.ucl.ac.be
Phone : 010/47 29 71

Selective cellular interaction with polymeric materials via their covalent coupling to integrin ligands.
 

 Integrins are with cadherins, selectins and immunoglobulins, part of the adhesion molecules family. They are transmembrane glycoproteins composed of two noncovalently associated heterodimers, designated as the a and b subunits. They are at least 23 different integrins which mediate cell-cell and cell-matrix interactions. These events provide effects as diverse as cell anchorage and migration, cell growth and differentiation, apoptosis, protein synthesis and gene expression.

Each integrin heterodimer may interact with one or more ligands, that are usually extracellular matrix compounds, and induce many different biological functions.

Since many years, the laboratory is interested in the design and the development of smart polymeric materials with a view to control the behaviour of mammalian cells. Selective surface modifications of the materials allow the covalent grafting of biologically active molecules acting as integrins ligands. The aim of this current work is to filtrate whole blood via modified filtration membranes in order to get leukocyte free samples.

We are interested in the a4b1, a4b7 and b₂ integrins, which are massively expressed on leukocytes. It has been demonstrated that these two first integrins recognize the LDV active sequence present in their natural ligands, while the b₂ familly has its own active sequence: the LLG tripeptide. 

We have performed the synthesis of a capped-tripeptide (LDV), armed with a PEG spacer to proove the feasibility of this project. We have turned then towards peptidomimetics of this sequence. On the other hand, the LLG sequence has also been synthetized in order to reach the b₂ integrins aswell.

Wet chemistry, i.e. chemical reaction carried out at the solid-liquid interface, is used for the  covalent grafting of the synthetizied compounds. The chosen materials are PBT and PVDF  commercial membranes.

The modified membranes are then characterized with radiolabelling (LSC), microscopy (SEM) and XPS. The membranes will finally be evaluated for their selective retention ability of leukocytes by flow cytometry measurements.