UC Riverside

Recent advancements in life science research have greatly improved our understanding of various intricate biological systems, some of which are affiliated with complex diseases. While a great deal of progress has been made towards the comprehension of relevant biophysical interactions, many remain poorly understood. This is especially true for protein interactions involving the cellular membrane. Of the analytical strategies developed for investigating molecular interactions, surface plasmon resonance (SPR) provides marked technical advantages and has become a cornerstone for these studies. However, the SPR method is still facing challenges, from both technical aspects and investigation of diseases, which are the focus of this Dissertation. SPR is susceptible to misidentification in biological matrices, due to cross-reactive and nonspecific interactions. The lack of reliable curved biomimetic membrane platforms has limited the investigation on various disease related protein interactions. The presented Dissertation aims to provide solutions to these challenges through developing novel biomimetic membrane platforms, robust post data acquisitions analysis strategies, and antifouling protocols. Chapter 2 showcases the development of a self-assembled pseudo-myelin sheath microarray. The platform and developed antifouling protocol were shown to be capable of detecting three multiple sclerosis (MS) specific anti-ganglioside antibodies in 10 % serum. Chapter 3 expands and improves upon the platform presented in Chapter 2. The MS specific antibodies were detected at disease relevant concentrations, 3 ng/mL to 25 ng/mL, in undiluted human serum. Machine learning algorithms were applied to facilitate the differentiation and identification of the highly cross reactive analyte-antigen interactions in a clinical setting. In Chapter 4, the characterization and development of a tunable curved membrane mimicking platform is presented. Through the use of statistical analysis, simulations, and SPR, we have demonstrated that the curved membrane platform could be uniquely applied to quantify protein-membrane interactions that require curvature. Chapter 5 reports the use of the curved membrane platform for the investigation of bridging-integrator-1’s biophysical interactions, and their detection in biological fluids such as urine, which has been affiliated with muscular dystrophy. This study is the first quantitative evaluation of these interactions, and could aid in the diagnosis of muscular dystrophy. The works presented in this Dissertation have laid a solid foundation for advanced SPR biosensing that focuses on biomarker detection and disease diagnosis.