Hyun-Ro Lee, Ph.D.
visualizing the dynamic reorganization of biological membranes in vital functions
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About Me
About Me
Hello, colleagues!
My name is Hyun-Ro Lee, and I'm currently a postdoctoral researcher at the University of California, Berkeley.
My primary research areas are Biomolecular and Chemical Engineering, Bio-interfacial Science, Biocolloids, Biomaterials, Membrane Biophysics, and Membrane-based Therapeutics.
In particular, my research has focused on understanding the spatiotemporal reorganization of biological membranes (e.g., cell membranes, lung surfactant membranes, and skin lipid matrix) using diverse techniques that enable in situ real-time visualizations of dynamic interfacial processes of biological membranes.
I aim to correlate membrane remodeling and cellular functions in the long run, discovering the general principles that control the self-assembly or self-organization of membrane biomolecules during cellular processes. This understanding should lead me to manage cellular functions as well as identify strategies for effective therapeutic intervention.
Professional Experience & Education
Postdoc in Chemistry, UC Berkeley (09/2023 – present)
Postdoc in Materials Science and Engineering, POSTECH (09/2021 – 08/2023)
Postdoc in Applied Science Research Institute, KAIST (09/2020 – 08/2021)
Ph.D. in Chemical and Biomolecular Engineering, KAIST (09/2016 – 08/2020)
M.S. in Chemical and Biomolecular Engineering, KAIST (09/2014 – 08/2016)
B.S. in Chemical and Biomolecular Engineering, KAIST (02/2010 – 08/2014)
Honors and Awards
PIURI postdoctoral fellowship ($25K/year), POSTECH (2022 – 2023)
Postdoctoral Training Grants ($51K/year), National Research Foundation of Korea (2021 – 2023)
G-CORE Research Project Awardee ($81K), KAIST ITVC, Ministry of Science and ICT (2021)
Government-sponsored Scholarship, Korean Government (2016 – 2020)
Best Poster Award, Korean Society of Industrial and Engineering Chemistry (2017)
Individual Research Program Awardee for the Realization of Graduate Students’ Creativity ($4.5K), KAIST College of Engineering (2015)
First prize ($8.9K), GS Caltex-KAIST Outstanding Research Competition (2014)
National Science & Technology Scholarship, Korea Student Aid Foundation (2012 – 2013)
Representative Publications
Hyun-Ro Lee et al., Lipid Droplet Surface Promotes 3D Morphological Evolution of Non‐Rhomboidal Cholesterol Crystals, Advanced Science, 2025
Hyun-Ro Lee et al., Sphingomyelinase-Mediated Multitimescale Clustering of Ganglioside GM1 in Heterogeneous Lipid Membranes, Advanced Science, 2021
Hyun-Ro Lee et al., Ultra-stable Freestanding Lipid Membrane Array: Direct Visualization of Dynamic Membrane Remodeling with Cholesterol Transport and Enzymatic Reactions, Small, 2020
Hyun-Ro Lee et al., Irremovable Blood Stain in Lung: Air-to-Interface Transport of Albumin and Its Mechanical Response to Biaxial Compression/Expansion, ACS Applied Bio Materials, 2019
Hyun-Ro Lee et al., A new method to produce cellulose nanofibrils from microalgae and the measurement of their mechanical strength, Carbohydrate Polymers, 2018
My Research
My Research
Self-assembly and reorganization of membrane biomolecules govern cellular processes, including cell signaling, differentiation, and cell growth. However, the mechanism of dynamic remodeling in the biological membranes and cell-cell interfaces is still largely underdeveloped. This issue has led me to raise the following questions step by step:
1. What are the underlying principles that control the self-assembly (equilibrium, optimization) and self-organization (dynamic order, dissipation) of biomolecules in biological membranes?
2. How are dynamic remodeling of biological membranes correlated with cellular processes?
3. Can we control cellular functions for biomedical applications by manipulating the organization of biological membranes?
To answer these questions, I aim to understand the spatiotemporal redistribution of the biomolecules in the biological membranes and cell-cell interfaces at molecular- to micrometer scales using state-of-the-art visualization techniques. This imaging technique uniquely allows me to understand the mechanisms of the cell functions and discover practical strategies for diverse biomedical applications. A brief demonstration of my studies is shown in the following:
In situ real-time visualization of dynamic membrane remodeling
We have developed a technique that enables in situ real-time visualizations of dynamic membrane remodeling, called freestanding planar lipid membrane array (H.-R. Lee et al., Small, 2020)
In this model membrane system, tens of freestanding planar lipid membranes are formed in the hexagonal TEM grid holes, supported by the lipid-containing oil like a black lipid membrane system.
The formation process of the lipid membrane in the hexagonal TEM grid hole. Its shape is round in the beginning but becomes more and more hexagon as time passes.
Dynamic remodeling of the lipid bilayer membranes by temperature variation
The lipid membranes exist as a single liquid phase above the melting temperature, but they can be phase-separated into two phases below the melting temperature. The membrane phase behaviors significantly vary with the membrane composition, particularly cholesterol.
Separation of the lipid membrane into the gel and liquid phases by cooling. The lipid membrane consisting of DOPC and DPPC (~1 mol% TR-DHPE) is divided into the gel and liquid phases via nucleation-and-growth.
Mixing process of the gel and liquid phases in the lipid membrane by heating. The lipid membrane phase-separated into the DPPC-rich gel and DOPC-rich liquid phases changes into a single liquid phase by heating.
Separation of the lipid membrane into two liquid phases by cooling. The lipid membrane consisting of DOPC, DPPC, and cholesterol (~1 mol% TR-DHPE) is divided into the liquid-ordered and liquid-disordered phases via nucleation-and-growth.
Mixing process of two liquid phases in the lipid membrane by heating. The lipid membrane phase-separated into the DPPC/cholesterol-rich liquid-ordered and the DOPC-rich liquid phases changes into a single liquid phase by heating.
Dynamic remodeling of the lipid bilayer membranes by cholesterol transport
The lipid membranes dynamically undergo phase transition by cholesterol transport. Using a representative cholesterol carrier, methyl-beta-cyclodextrin, we can control the cholesterol content in the lipid membranes. The detailed demonstration on each video is introduced in H.-R. Lee et al., Small, 2020.
The phase transition from gel to liquid-ordered phase in the DOPC/DPPC membrane by cholesterol addition. 20-30 mol% of cholesterol was included in the lipid membrane.
The phase transition from gel to liquid-ordered phase in the DOPC/sphingomyelin membrane by cholesterol addition. 20-30 mol% of cholesterol was included in the lipid membrane.
Mixing of gel and liquid phases into one liquid-ordered phase in the DOPC/DPPC membrane by cholesterol addition. More than 40 mol% of cholesterol was included in the lipid membrane.
Nucleation of cholesterol crystals from the DOPC/DPPC/cholesterol membrane by cholesterol addition. More than 70 mol% of cholesterol was included in the lipid membrane.
Phase separation of the lipid membrane by slow cholesterol extraction.
Phase separation of the lipid membrane by fast cholesterol extraction.
Phase separation of the lipid membrane via spinodal decomposition.
Dynamic remodeling of the lipid bilayer membranes upon sphingomyelinase-mediated reaction
Sphingomyelinase (SMase) is an enzyme that hydrolyzes sphingomyelins present in the outer cell membrane leaflet to ceramides. The SMase-mediated reaction induces the clustering of membrane receptors (e.g., CD95, CD40, ganglioside GM1, and CFTR) into the local microdomains, thus initiating cell signaling, such as apoptosis. We visualized the SMase-induced membrane remodeling to understand how SMase-mediated hydrolysis causes receptor clustering (H.-R. Lee et al., Adv. Sci., 2021).
Schematic illustration of SMase-induced clustering of membrane receptors
The remodeling of the DOPC/ESM/cholesterol membrane upon sphingomyelinase-mediated hydrolysis. Interestingly, two different domains are newly created in the lipid membranes, and they induce receptor clustering in different spatiotemproal scales. The detailed demonstration on this video is shown in H.-R. Lee et al., Adv. Sci., 2021.
The remodeling of the DOPC/ESM membrane upon sphingomyelinase-mediated hydrolysis.
Displacement of the lung surfactant membrane by ultra-stable albumin film
The blood inflow into alveoli inactivates lung surfactants laden at the air-water interface of alveolar surfaces, which may lead to acute respiratory distress syndrome (ARDS). It is well-known that serum proteins dissolved in the aqueous subphase are rapidly adsorbed on the air-water interface by diffusion, thus displacing the lung surfactants. However, what if serum proteins are transferred from air to the air-water interface? This could happen when patients experience bronchitis, bronchogenic carcinoma, and chest trauma. Therefore, we visualized how serum proteins (e.g., albumin) displace the model lung surfactants as they dropped from air into the air-water interface (H.-R. Lee et al., ACS Appl. Bio Mater., 2019).
Schematic illustration of transport of serum proteins to air-water interface in alveoli
The formation of the petal-shaped albumin film at the air-water interface
Structural change in petal-shaped albumin film upon biaxial compression and expansion
High stability of petal-shaped albumin film upon biaxial compression-expansion cycles
Phase transition of skin lipid matrix
The skin lipid matrix in the stratum corneum is essential for a physical skin barrier that prevents external materials from our body. It has multilamellar lipid bilayer membranes mainly composed of ceramides, cholesterols, and free fatty acids. Therefore, manipulating the phase behaviors of the skin lipid matrix may enable an on-demand control of the barrier function and skin permeability, but the underlying principles of the phase transitions in the skin lipid matrix remain unclear. To understand these principles, we observed the phase behaviors of the model skin lipid matrix using a supported lipid membrane technique.
The phase separation of the model skin lipid matrix.
The phase transition of the model skin lipid matrix by applying the cosmetic emulsion that contains cyclodextrins.
Curriculum Vitae (CV)
Curriculum Vitae (CV)
Contact Information
Contact Information
Office: 424 Stanley Hall, Berkeley, CA 94720
Email: lhyunro@berkeley.edu / lhyunro@gmail.com
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