With the rapid development of nanotechnology, engineered nanoparticles (NPs) may be released to the environmental and biological systems either purposely or accidentally. With many proteins enriched in the environmental and biological media as the functional building blocks, they can be absorbed onto the NP surface, forming the so-called NP-protein corona. It is the protein coronae rather than the original NPs that are "seen" by cells and tissues and subsequently determine the biological and/or pathological functions of these released NPs. The objective of this proposal is to develop and apply state-of-the-art computer simulation methods to understand the fundamental aspects of the corona formation and to determine the physical and chemical properties of NPs that dictate the protein absorption. The obtained knowledge will help guide the design of novel NPs that promotes the intended biological functions and prevents the unintended pathological responses, enabling the "safe-by-design" to the broad scientific and engineering community for modeling and predicting corona formation and rapid risk assessment of NP exposures.
In this CAREER proposal, the PI proposes to apply the multiscale discrete molecular dynamics (DMD) methodology to characterize the structure and dynamics of NP-protein corona and to identify the physicochemical determinants of the NP-protein interactions. The objective of this research will be accomplished by pursuing the following specific aims: 1) Develop NP models and their interactions with biomolecules for DMD simulations; 2) Uncover the physicochemical determinants of NP-protein binding; 3) Characterize the structure and dynamics of protein aggregation in the corona; and 4) Extend the research and education in classroom and laboratory more broadly to other education and scientific research community. The developed and validated computational methodology will be shared with the broad scientific research communities. The proposed research projects will uncover the structural and dynamic properties of NP-protein corona at the molecular and atomic level and determine the physicochemical determinants of the molecular complex formation. The obtained results from the proposed mechanistic studies will be pivotal in designing more efficient and safe NPs with optimal properties to promote intended biological functions and minimize the pathological implications of NP exposure.
Broader impacts of this proposal include the sustainable development of nanotechnology and improves applications of nanomedicine. Funding of this research will also support students training at the interfaces of physics, material science, biology, and environmental science and engineering, update physics curriculum to reflect the current trend in science, and increase the diversity of physics education and research. The proposed research will develop and validate critical predictive tools to effectively and efficiently model the nano-bio interface, which can be used for engineering NPs with novel biological functions as well as for NP risk assessment. In addition, easy accessibility and enhanced usability of the developed tools will benefit the broad science and engineering community working in the field.
