Chemical pericellular modification for control of cell behavior

Abstract

Cells determine their behavior from the information gathered from their surrounding environment, which is called pericellular space. The pericellular space means the space near individual cells, including physical environment (i.e. contact with other materials, cells or air, pressure, hardness, osmotic pressure) and chemical environment (i.e. ions, growth factors, specific chemicals), and the cell membrane. Cell membrane receive and gather the information with numerous receptors, or become a signal channel by controlling the molecule transportation. Cells move and differentiate based on the information and sometimes secrete factors for signal transmission or enzymes to modify environment. So, using this in reverse, a technique for controlling cell behavior by manipulating pericellular environment has been intensively studied in chemistry and biology. When manipulating the pericellular environment, not only the purpose of manipulation, but also the environmental change during the cell culture and cytocompatibility should be considered. In this thesis, we developed the chemical methods using lipids and inorganic materials for controlling cell behavior, and cell interactions that can be seen in nature were reproduced and studied through the method. First, method for cell patterning was developed and homotypic and heterotypic cell-cell interactions were studied. Cell attachment can be controlled by the charge of lipid molecules, and lipid bilayer structures are collapsed when they are exposed to air. So, we made a lipid-protein pattern with microcontact printing method and zwitterionic lipids, attached the cells on the protein pattern, then washed away the zwitterionic lipid bilayer by exposing the substrate to the air. After the lipid collapse, homotypic or heterotypic cells were seeded, cultured and their interactions were studied. Next, we developed the method for single-cell nanoencapsulation with porous titania and applied it to T cell and astrocytes. Titania-inducing, cationic peptides were attached to cells by electrostatic interaction and precursor of titania was treated. Repeated process made the porous titania shell around the cell. As-made porous titania protected T cells from low or high temperature, but did not hampered the receptor-ligand and juxtacrine interaction. Furthermore, when astrocytes were encapsulated with titania, they differentiated to a new kind of reactive astrocytes. In brief, we developed the chemical pericellular modification methods for controlling the cell behavior, and studied cell-cell and cell-cell interactions through the methods. Although the methods were applied to the limited cell species in this thesis, we expect they are applicable through wide range of cell species and substrates, which can be used as a basis for understanding cell behavior.