本研究利用本實驗室長期建立之Isothermal Titration Calorimetry （ITC）、 Surface Plasmon Resonance(SPR)及Molecular Modeling(MM)來探討Poly ethylene glycol(PEG)及 phospholipid(如PC)分子改質之蛋白質及生醫材料於生物系統中與生物分子之作用行為機制。研究結果期望說明為何PEG 與PC 分子之作用而延長PEG 或PC 改質之生物分子於生物體內循環時間(Circulation Time )及生醫材料之anti biofouling 行為。 Poly ethylene glycol(PEG)及phospholipid(如PC)改質之生物分子(如蛋白質，微脂粒)或生物材料等ㄧ般皆發現有於生物系統內避免生物系統(如免疫系統)之攻擊與排斥、降低 peptides、proteins 或macrophages 等生物分子之吸附(Biofouling)、改變藥動學機制、延長生理循環時間及提高生物相容性之 in vivo 之表現等現象，而此性質也廣為運用於不同領域。如PEGylated 「 Stealth」微脂粒，如」Compatibles」，隱形眼鏡，如PEGylated α-Interferon-alpha 2a 之藥物控制釋放等。但這些因PEG 或phospholipid 改質之生物物質之生體表現行為卻未被真正深入瞭解其與生物分子之作用，及因PEG 或PC 改質之應用相當廣泛，所以文獻資料也分佈於不同之領域與知識庫中，不同領域所累積之知識，因研究對象與內容不同，造成研究成果之相互驗證缺乏了共同研究條件而無法廣泛交流以致此生物改質材料之應用仍只侷限於實驗結果之報導，並無法深入其機制，以致能提供更佳之操作條件(生醫材料之應用)及進而能以分子工程，分子設計之角度提供更佳之改質PEG 或PC 及新分子結構。本研究之重點將強調於水分子、氫鍵之形成與破壞、親疏水性作用力(hydrophobic interactions)與改質分子之結構與排列之角色來研究生物分子及改質分子之水合能力 (hydration and dehydration)之競爭與其於生物系統應用之相關性為主。實驗之重點除探討蛋白質吸附外也將進一步培養細胞以說明材料改質、蛋白質吸附、及細胞吸附及angiogenesis 之關係。以期提供此分子間作用機制及新分子設計之理論基礎。 The poly(ethylene glycol) (PEG) or phospholipids modified protein and surfaces have been used for various biomedical and bioengineering applications. However, the relations to physico-chemical properties and mechanisms of the interactions of the PEG and phospholipids modified proteins and surfaces with biological system have not been well studied. Our attempt, in this study, is to use our long built experience on isothermal titration calorimetry (ITC), surface plasmon resonance (SPR) and molecular modeling (MM) to target the interaction mechanism between biomolecules in biological system with the modified proteins and surfaces. The main emphasis will be on the role of water molecules, the hydrogen bonding, the hydrophobic interaction and hydration and dehydration of the biomolecules and PEG and phospholipids modified protein and surface. The packing orientation and density of the PEG and phospholipids will be studied in detail, as well. The protein adsorption and cell culture and angiogenesis will be performed to validate the investigation. This investigation is needed to rationalize the widely varying findings in different area of applications. The objective of this study is to provide the fundamental information for biomaterials modification for biomedical applications and also to provide rational design idea for any new molecules for the biomedical applications purposes. 研究期間：9608 ~ 9707
