Rapid and Direct Cell-to-Cell Adherence Using Avidin-Biotin Binding System: Large Aggregate Formation in Suspension Culture and Small Tissue Element Formation Having a Precise Microstructure Using Optical Tweezers

Abstract

Effectively organizing isolated cells to tissue elements having an appropriate microstructure is a fundamen-tal issue in future tissue engineering, but biological cell-to-cell adhesion is too weak to assemble single cells directly. In order to overcome the difficulty, we applied an Avidin-Biotin Binding System (ABBS) to cell surfaces, and avidinylated and biotinylated cells could mutually bind in the short time they were mixed to-gether. Unlike conventional intact cells, ABBS helped make larger spheroids. Interestingly, avidinylated and biotinylated cell adherence occurred within 1 sec using laser trapping, enabling single cell manipulation. We showed precise, direct single-cell-based tissue assembly using ABBS and optical tweezers, followed by damage-free tissue culture. The combination of ABBS and single cell manipulation has considerable potential for use in application such as tissue engineering, regenerative medicine, and drug screening system.