Research Overview

Our research is profoundly interdisciplinary, with a primary focus on unraveling the sequence/composition-structure-function relationship of biomolecules (including proteins and peptides) when interacting with biomaterials, biomembranes, and inorganic surfaces.

We employ a unique approach that integrates theoretical models, molecular simulations, and biophysical experiments to advance transformative biomaterial research. Our investigations span from fundamental inquiries to practical applications, encompassing scales ranging from nano to macro.

Our overarching goal is to enhance our understanding of biophysicochemical interactions between biomaterials and biomolecules, with the aim of facilitating their transformative applications in biomedicine and engineering. Currently, our research projects are centered around the following areas of interest:

Amyloid Peptides Associated with Neurodegenerative Diseases

Amyloid peptides, such as Aβ associated with Alzheimer's disease, hIAPP with type II diabetes, α-synuclein with Parkinson's disease, and over 20 other peptides, exhibit an intrinsic propensity to form β-sheet-rich aggregates of varying molecular sizes, which are highly cytotoxic to cells. However, the mechanisms underlying the formation of these amyloid aggregates and their induction of cytotoxicity in neuronal cells remain largely elusive. The lack of atomic-level details regarding amyloid oligomeric structures and their interactions with cell membranes presents a significant challenge in comprehending the biological roles of amyloid oligomers in aggregation and toxicity mechanisms. Additionally, this hinders the rational design of structural-based inhibitors and probes against amyloid diseases.

We combine a variety of biophysical techniques and computational approaches to achieve several key objectives in our research. Firstly, we aim to determine atomic-resolution structures of amyloid oligomers with different sequences. Additionally, we investigate the complete adsorption and aggregation process of amyloid peptides, along with their membrane disruption mechanisms in the presence of cell membranes. Furthermore, our research involves designing small organic molecules, nanoparticles, and peptides as inhibitors to prevent amyloid aggregation and mitigate toxicity. We also explore the repurposing of existing drugs currently used for cardiovascular disease and high blood pressure as potential amyloid inhibitors. Moreover, our investigations extend to examining cross-seeding interactions between amyloid proteins and other disease-related proteins, such as antimicrobial peptides and cancer proteins. By uncovering molecular links and spreading mechanisms across different diseases, we aim to gain insights into the broader implications of amyloid aggregation. Additionally, we develop aggregation-induced emission (AIE) and fluorescent molecules as probes for the early detection of amyloid proteins. Overall, our primary objective is to provide a comprehensive and fundamental understanding of the molecular mechanisms governing amyloid structure, toxicity, inhibition, and detection across different pathological pathways.

Smart and Tough Hydrogels

Many hydrogels suffer from mechanical brittleness and weakness, which limits their broad applicability. In our work, we leverage molecular simulations and experimental techniques to develop a series of physically-linked double-network hydrogels using innovative design strategies and synthesis methods. Our goal is to create hydrogels that fulfill several key requirements:

By addressing these objectives, we aim to overcome the limitations of conventional hydrogels and pave the way for their widespread use in diverse fields.

Multifunctional Biomaterials

The design and synthesis of highly bioinert and biocompatible antifouling materials are critical for numerous fundamental and practical applications. To address this need, we have developed a computational-data-driven platform that enables us to test design principles and rationally engineer new antifouling materials. Leveraging computational design, we have synthesized and evaluated a diverse range of biomaterials, including polyacrylamide/acrylate-, polyethylene glycol (PEG)-, and zwitterionic-based polymers. These materials have been utilized for various applications, such as antifouling surfaces and coatings, antifouling wound dressings, antifouling nanogels, and antifouling and antimicrobial hydrogels. Additionally, our research encompasses the investigation of antifouling biomimetic nanochannels, polymer-protein interactions, the fundamental mechanisms underlying antifouling properties, and the development of tough and self-healing hydrogels. Through these efforts, we aim to advance the field of antifouling materials and contribute to the development of innovative solutions for biomedical and industrial challenges.

Engineering Biomaterials for Biomedical Applications

In order to address a wide range of biomedical requirements, spanning from laboratory research to clinical application, we have engineered smart zwitterionic polymers. These polymers are tailored with various stimuli-responsive groups and are formulated into different formats, including nanogels, hydrogels, brushes, and fibers. Our aim is to deploy these innovative materials for applications such as wound dressing, substitutes for contact lenses, and drug/gene delivery systems. By offering versatile and adaptable solutions, we strive to enhance healthcare outcomes and improve patient well-being. 

Development of Advanced Computational Algorithms and Models

we are the forefront of the development of highly efficient and precise computational techniques, particularly tailored for intricate biomolecular systems. These cutting-edge methodologies and models serve as a crucial bridge between nano- or microscopic simulations and macroscopic observables. Our computational toolkit encompasses a diverse array of techniques, including: