Preview

PDF, English Download (17MB) | Terms of use

Abstract

Integrin-mediated cell-extracellular matrix (ECM) adhesion and cadherin-mediated cell-cell adhesion are two main interactions that exist in organism. In order to exclude complex interference in living organism to study how these specific interactions affect cell behaviors, integrin ligands or cadherin ligands can be isolated and immobilized on/in biomaterials. In this thesis, integrin ligand RGD peptide and/or E-cadherin ligand HAV peptide were immobilized on 2D surfaces to study the cell adhesion force and the adhesion mechanisms. In part I, cell adhesion force induced by integrin-RGD interaction was studied based on the technology of nitrogen-vacancy (NV) diamond. RGD peptide, which was connected to paramagnetic ion Gd3+, was immobilized onto the NV diamond through PEG chain, generating an NV diamond based force sensor. Spin-spin coupling between Gd3+ and NVs dependent photoluminescence was recorded as a signal when cell traction force exerted. Different immobilization methods were developed, in order to obtain an optimized chemical structure for the force sensor. Cell traction force generated by integrin-induced adhesion was presented as relaxation time T1 map within a cell region. In part II, E-cadherin mimetic HAV peptide was immobilized on continual gold surface or nanopatterned gold surfaces in order to precisely control the immobilized amount. HAV-E-cadherin interaction induced cell adhesion was then studied. The results revealed that the surface immobilized HAV peptide specifically interacted with E-cadherin from cells, inducing the translocation of E-cadherin based adhesion from adherens junction at cell-cell interface to HAV-E-cadherin binding at cell-material interface. This leads to enhanced cell adhesion on the material surfaces and weakened cell-cell contact, which could play important role in wound healing. The HAV-E-cadherin interaction was proved to activate β-catenin signaling pathway, which was the same as E-cadherin based adherens junction at cell-cell interface. These studies according to cell-ligand interactions on specific ligands are helpful to understand the mechanisms of cell adhesion and cell-materials interactions, which also provide new information about cell behavior on biomaterials. These results can be important in the design of new biomaterials. NV diamond based force sensor with respective ligand can be considered as a prospective toolbox to investigate different types of cell adhesions. For example, the HAV peptide in the second section can be included to detect the force of E-cadherin-induced cell-cell adhesion.