Sun Lab
Project 1: Emergent molecular processes when interfacing biomembranes with liquid-liquid phase separation
An initially homogeneous aqueous system of biomolecules (or polymers) can separate into two distinct phases, depending on solute concentrations, temperature, pH, etc. This physical process, termed as liquid-liquid phase separation (LLPS), is ubiquitous and has been recognized as a key player in both cell biology and materials science, and it may have contributed to the origins of life. Some LLPS processes occur on biomembranes and play critical roles in cell signaling, such as LAT protein condensation phase transitions during T cell receptor signaling. Intriguingly, when protein condensation phase transitions interface with a 2D membrane surface, they exhibit unique features that differ significantly from LLPS in bulk solutions, both thermodynamically and kinetically. Of particular interest, the two separated liquid phases may have distinct water structures, ionic concentrations, and pH values. We study how molecular processes at the biomembrane are regulated after interfacing with an LLPS system. Furthermore, we explore how the biophysical properties of biomembranes modulate phase transitions of proteins related to neurodegenerative diseases.
Project 2: Decoding extracellular vesicles-based grammar in noncontact intercellular communications and disease progression
Cells release bioparticles, membraneous or membraneless, to facilitate noncontact intercellular communications. Among these particles, small extracellular vesicles and nanoparticles (sEVPs) in the size range of approximately 30 nm to 150 nm are abundant in many human body fluids. Bulk analysis reveals that sEVPs carry a variety of biomarkers, including proteins, lipids, miRNAs and metabolites. Furthermore, genetically and chemically engineered sEVPs demonstrate high biocompatibility and can cross the bloodbrain barrier. These characteristics position sEVP as promising candidate for liquid biopsies and as therapeutic tools. One current major bottleneck is sEVP’s heterogeneity – these particles originate from different cell types, and even when secreted by the same cell type, their diversity can arise from different cargo sorting mechanisms and dynamic cellular states. Such complexity poses major obstacles to our understanding of the composition and functional properties of specific sEVP subtypes, thus impeding the specificity and sensitivity of any sEVP-based theranostic assays. We conduct quantitative characterizations of sEVPs at the single-particle level and unveil the distinct molecular features of each sEVP subtype. Such insights will facilitate the development of sEVP-based liquid biopsies and provide quality control methods for therapeutic tools utilizing sEVPs. Furthermore, we intend to analyze single sEVPs at the cell-cell interface, where disease-related information is transmitted, can elucidate the biophysics of sEVP signaling and the mechanisms of sEVP-mediated diseases.
Project 3: Unraveling the environmental information encoded in the physicochemical, biochemical, and optical properties of individual sea spray aerosols
Sea spray aerosol particles (SSAs), formed through wave breaking at the ocean surface, are the largest source of natural aerosols to Earth’s atmosphere on a mass basis. They exhibit significant heterogeneity in terms of size, composition, phase state and material properties. As the ‘messengers’ between the ocean and the atmosphere, SSAs affect climate directly by interacting with incoming solar radiation, as well as indirectly by influencing cloud formation. SSAs contain highly enriched organic matters, including active enzymes, compared to bulk seawater. Additionally, they can encapsulate viruses, bacteria and chemicals originated from polluted coastal waters, potentially leaving the coastal community directly exposed to sea-borne pollutants and pathogens. Previous reports have shown changes in atmospheric properties in regions where biological processes and chemical composition in the marine boundary layer are altered, however, it is still not clear how specific climate-relevant properties are encoded in the fundamental physicochemical properties, material attributes, and biochemical activities of SSAs. Furthermore, the global society has been constantly combatting global warming and ocean pollution like plastics, oil spills, and shipping emissions, etc. It is crucial to understand whether these consequences of human activities could alter the properties of SSAs, thereby exerting far-reaching impacts on regional climate and community health. Considering that SSAs are highly dynamic, non-equilibrium microdroplets exhibiting unique microphysical, biochemical, and optical properties relative to bulk systems, we perform comprehensive interrogations at the single-SSA level from the physical chemistry perspective and provide direct and quantitative answers to the above critical questions.
