Research On The Mechanism Of Topography-Coupled-Mechanics In Tumor Associated Biointerfaces

Tumor associated biointerfaces include not only interface between tumor cells ortissues and tumor microenvironment, but also the2D or3D interface between tumorcells and artificial materials. Both the molecular constituents and mechanical factors onthe biointerface play a key role during tumor genesis and progression. Presently,research on the tumor associated biointerfaces has been mainly focused on themolecular mechanism, however overlooking the effect of biomechanical factors, such asstiffness and topography. Hence, based on the biomechanopharmacology andTopography-Coupled-Mechanics, we focused on mechanical properties of thebiointerfaces and their application in cervical cancer early diagnosis, pharmacology ofantitumor agents and design of the antitumor drug carriers.Polydimethylsiloxane (PDMS), polyacrylamide hydrogel (PAAG) andpolycaprolactone (PCL) were used for the biomimetic fabrication based on mechanicalproperties of biointerfaces. Atomic force microscope (AFM), confocal scanning lasermicroscope and environmental scanning electron microscope (ESEM) were employedfor the mechanical characterization and analysis of the tumor associated biointerfaces.Firstly, we found that stiffness of morphologically normal squamous cells (MNSCs)correlated well with cervical malignancy, and may have potential in cancer screening toprovide early diagnosis. Besides, stiffness of the tumor associated biointerfaces not onlyincreased proliferation of tumor cells, but also had a joint pharmacological effect withantitumor drugs, in which cytotoxicity of the drugs was increased on rigid substrate.The altered sensitivity of tumor cells was due to the rapid progression of cell cycleresulted from the increased phosphorylation of tyrosine397in focal adhesion kinase onthe rigid substrate. Furthermore, we found that adhesion behavior of tumor cell could begreatly influenced by the topography of pollen-mimetic microspheres. When increasingthe pore size on surface of the microspheres, the adhesion on tumor cells wassignificantly improved, indicating that tumor cells could be topographically binded bycontrolling the surface topography of bioadhesives.According to above results, the biomechanical properties of tumor associatedbiointerfaces could find their applications not only in the process of tumor earlydiagnosis, but also in fields of antitumor drug screening, chemotherapy and even design of antitumor drug carriers. Prospectively, research on the biomechanopharmacology andTopography-Coupled-Mechanics in tumor associated biointerfaces will provide a newavenue for exploring the mechanism of tumorgenesis and the way of cancer treatment.