精妙な生体膜のはたらきとナノバイオマテリアルの開発

抄録

Biological and biophysical understanding of cellular functions and machinery will provide a variety of insights into design and synthesis of materials and devices. For instance, shielding of the cell surface can block some of cellular recognition processes and is a useful technique to protect cells and tissues against the harmful substances. By using water-soluble and nonionic polymers having a lipophilic anchor group at one end, polymer chains were attached to a cell surface through the hydrophobic interaction. Alternatively, polymer chains could be chemically linked to membrane proteins or saccharides. Furthermore, cell modification could be carried out using polymer chains with affinities such as RGD-integrin. In all the cases, activation of modified cells was suppressed when they met with relatively large materials such as a tissue culture dish and a micrometer-sized latex particle. Another cell surface engineering is associated with the signal transduction through cell membrane receptors. In signaling process, the signaling appears to emerge from the dynamic motions such as clustering and patterning of distribution of proteins and other molecules in the membrane. Neutrophils were coupled to thermosensitive polymer chains with cell-adhesive RGD peptides. The cells became activated when the temperature was raised. This modification makes it possible to induce the specific activation by clustering of receptors through the polymer association. Nanoparticles can be prepared by the interchain aggregation or the chemical cross-linking of polymer chains. We developed a novel drug delivery system for apoptosis induction by a “smart” polymer vehicle possessing thermo-sensitivity and bioaffinity. The polymeric nanoparticles incorporating an apoptotic inducer, dol-p, were added to a human promonocytic leukemia U937 cell suspension at 37°C. By lowering temperature to 25°C, cells underwent apoptosis in the presence of Ca²⁺. This technique would allow cells to possess the ability to induce apoptosis in response to stimuli such as temperature. Such engineered cells would be expected for the gene therapy, the cytomedical therapy, and the tissue engineering.